139 results on '"Lionnel Geoffrois"'
Search Results
52. TPExtreme randomized trial: Quality of Life (QoL) and survival according to second-line treatments in patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC)
- Author
-
Jean Bourhis, Alison Claire Johnson, Anne Auperin, Caroline Even, Esma Saada-Bouzid, Raissa Kapso, Damien Vansteene, Ricard Mesia, Ulrich Keilholz, Helene Castanie, Olivier Capitain, Melissa Delhommeau, Didier Cupissol, Lionnel Geoffrois, Jérôme Fayette, Christian Sire, Gortec Aio Studien gGmbH Ttcc Unicancer H N, Laurent Martin, Cecile Chevassus-Clement, Cedrik Lafond, and Joël Guigay
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Taxane ,business.industry ,medicine.disease ,Head and neck squamous-cell carcinoma ,law.invention ,03 medical and health sciences ,Regimen ,0302 clinical medicine ,Second line ,Randomized controlled trial ,Quality of life ,law ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Overall survival ,In patient ,business ,030215 immunology - Abstract
6507 Background: TPExtreme trial comparing EXTREME regimen to the taxane-based TPEx confirmed the encouraging survival results of the TPEx regimen, despite lack of significant overall survival (OS) increase, with a significantly lower toxicity than the EXTREME regimen. Herein, the QoL and exploratory analyses of survival according to 2nd line treatments focusing on immunotherapy (IO) are presented. Methods: Randomized (1:1), open-label trial. Main inclusion criteria were R/M HNSCC not suitable for loco-regional treatment, age 18-70 years, PS < 2, creatinin clearance > 60ml/min, prior cisplatin < 300 mg/m². 539 pts were enrolled over a period of 37 months (mo). QoL was evaluated with QLQ-C30 questionnaire at baseline, week(W)12, W18, W26 and analyzed by linear mixed model. The primary QoL endpoint was the Global Health Status score. 2nd line treatments were collected for 501 (93%) patients (pts), 256 in the EXTREME arm and 245 in the TPEx arm. Results: The percentage of QLQ-C30 questionnaires filled at baseline, W12, W18 and W26 were similar in the 2 arms, 89%, 52%, 43%, and 39% in the EXTREME arm and 91%, 59%, 40%, and 37% in the TPEx arm, respectively.. Higher scores of Global Health Status (p = 0.02), physical functioning (p = 0.009) and role functioning (p = 0.013) and lower scores of appetite loss (p = 0.041) were observed in the TPEx arm than in the EXTREME arm. No significant difference was observed for the other scores. In 2nd line treatment, 120 (47%) pts in the EXTREME arm and 109 (44%) in the TPEx arm received chemotherapy +/- cetuximab (CT); 41 (16%) pts in the EXTREME arm and 41 (17%) in the TPEx arm received IO, mainly anti-PD-1/PD-L1. 79% and 85% of these 2nd line treatments were given after progression in EXTREME and TPEx arms respectively. Median OS (95%CI) since randomization was 17.6 (15.2 – 19.5) mo with CT and 19.4 (13.4 – 22.3) mo with IO in the EXTREME arm vs 14.9 (13.0 – 16.3) and 21.9 (15.9 – 35.0) mo in the TPEx arm (interaction test p = 0.077) respectively. Median OS since start of 2nd line was 9.3 mo with CT and 8.3 mo with IO in the EXTREME arm, and 7.1 and 11.6 mo respectively in the TPEx arm. Conclusions: An improvement in the QoL of patients was observed in the TPEx arm compared to that of the EXTREME arm. Exploratory analysis showed that the taxane-based TPEx regimen followed by IO in 2nd line could provide interesting median OS for pts who need CT in 1st line, with less toxicity than EXTREME. This sequential treatment deserves to be compared to a strategy that starts with Platinum+5FU+pembrolizumab. Clinical trial information: NCT02268695 .
- Published
- 2020
53. Evolving development of PD-1 therapy: Cetrelimab (JNJ-63723283) from monotherapy to combination with erdafitinib
- Author
-
Piotr Rutkowski, Salvatore Siena, Anne OHagan, Dariusz M. Kowalski, Carmen Beato, Victor Moreno, Enriqueta Felip, Scott T. Tagawa, Yohann Loriot, Emiliano Calvo, Begoña Mellado, Lionnel Geoffrois, Elizabeth Ruth Plummer, Ignacio Duran, Diego Cortinovis, Sydney Akapame, Manish Monga, James G. Greger, Nebedita Bandyopadhyay, and Arlene O. Siefker-Radtke
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Immune checkpoint inhibitors ,03 medical and health sciences ,0302 clinical medicine ,Erdafitinib ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,business ,030215 immunology - Abstract
3055 Background: Cetrelimab (CET) is an investigational checkpoint inhibitor (CI). In part 1 of a first-in-human (FIH) trial (LUC1001; NCT02908906), pts with advanced solid tumors with ≥1 prior treatment received CET 80–800 mg Q2W or 480 mg Q4W. Response rates and safety profiles were similar to other CIs. Based on preclinical and clinical data, a phase 1/2 study (NORSE; NCT03473743) of CET + erdafitinib (ERD) in metastatic urothelial carcinoma (mUC) + FGFR alterations (alt) was initiated and is ongoing. Methods: In LUC1001 Part 2, pts with nonsmall cell lung cancer (NSCLC), melanoma (MEL), or MSI-H/dMMR colorectal cancer (CRC) received CET IV 240 q2w. Overall response rates (ORR = % complete response + partial response [PR] confirmed) were assessed as per RECIST v1.1. Adverse events (AEs) were assessed for all patients receiving CET IV 240 q2w in parts 1 and 2. Results: As of July 1, 2019, 122 pts with NSCLC (n=30); MEL (n=50); or CRC (n= 42) had been treated in Part 2. Median age ranged from 58 to 64 yrs (overall range, 23–86 yrs). Duration of treatment was 8.1 mos (range, 0.0-24.7) for NSCLC; 5.5 mos (range, 0.0-25.0) for MEL; and for 3.0 mos (0.0-16.1) for CRC. ORR was 37% in NSCLC; 53% in PD-L1+ NSCLC (≥50% by IHC), 28% in MEL; 32% in non-uveal MEL, 14% in CRC and 24% in centrally confirmed MSI-high CRC. In all CET IV 240 q2w treated pts in the FIH study (N= 162), treatment-related grade ≥3 and serious AEs were reported in 15% and 12% of pts, respectively. All grade and grade ≥3 immune-related (ir) AEs were reported in 41% and 8% of pts, respectively Most common ir AE: hypothyroidism (8%), asthenia (6%), diarrhea (4%), rash (4%), hyperthyroidism (4%), dyspnea (3%), pruritis (3%) and pneumonitis (3%). There was 1 treatment-related death due to myasthenia gravis. In the phase 1 combination study (NORSE), pts with mUC + FGFR alt (n=17) received fixed-dose CET IV 240 q2w + ERD 6mg, 8 mg or 8mg + up titration (UpT) to 9 mg to establish the RP2D for the combination as CET + ERD 8mg + UpT. In the RP2D group (n=10), 60% had treatment-related grade ≥3 AEs. ORR (all confirmed PR) was 50% in the all treated response-evaluable group (n=16). Conclusions: CET is a CI with efficacy and safety profiles in advanced solid tumors similar to approved CIs. In NORSE phase 1, CET+ ERD demonstrated antitumor activity in mUC with an acceptable safety profile. NORSE phase 2 is evaluating this combination as first-line therapy in pts with mUC with FGFR alt. References: Rutkowski, et al J Clin Oncol.2019; 37 (8 suppl): 31-31. Moreno, et al. ASCO-GU Genitourinary Cancers Symposium. February 13-15, 2020. San Francisco, CA. Clinical trial information: NCT02908906 and NCT03473743 .
- Published
- 2020
54. Does escalation results from phase Ib/II Norse study of erdafitinib (ERDA) + PD-1 inhibitor JNJ-63723283 (Cetrelimab [CET]) in patients (pts) with metastatic or locally advanced urothelial carcinoma (mUC) and selected fibroblast growth factor receptor (FGFR) gene alterations
- Author
-
Victor Moreno, Arlene O. Siefker-Radtke, Yvonne Y. Lau, Begoña P. Valderrama, Salvatore Siena, Anne OHagan, Begoña Mellado, Mark D. Fleming, Lionnel Geoffrois, Sydney Akapame, Carmen Beato, Yann-Alexandre Vano, Scott T. Tagawa, Yohann Loriot, Ignacio Duran, and Jaszianne A. Tolbert
- Subjects
Cancer Research ,Metastatic Urothelial Carcinoma ,biology ,business.industry ,Locally advanced ,03 medical and health sciences ,0302 clinical medicine ,Oncology ,Erdafitinib ,Fibroblast growth factor receptor ,030220 oncology & carcinogenesis ,Programmed cell death 1 ,biology.protein ,Cancer research ,Medicine ,In patient ,business ,Gene ,030215 immunology ,Urothelial carcinoma - Abstract
511 Background: ERDA, an oral pan-FGFR inhibitor, is approved by the US FDA for pts with metastatic urothelial carcinoma (mUC) with susceptible FGFR3/2 gene alterations and progressed after ≥1 line of prior platinum-containing chemotherapy (PCC).1 CET, an IgG4, binds to anti-programmed cell death proteins (PD-1) and has shown activity in solid tumors.2 ERDA+CET may demonstrate complementary mechanisms as neoantigen release by ERDA may prime the tumor microenvironment for response. NORSE is a phase 1b/2 study to evaluate ERDA+CET in pts with mUC. Methods: Adult mUC pts with specific FGFR alterations who have progressed after ≥1 prior systemic therapy and no prior FGFR or PD-1/PD(L)-1 inhibitors enrolled in 3 dose levels (DL) of ERDA (DL1: 6 mg, DL2A: 8 mg, DL2: 8 mg with uptitration [UPT] to 9 mg) + CET (IV, 240 mg). Cohorts enrolled until dose limiting toxicity (DLT) or RP2D was identified. Primary endpoints: DLT and adverse events (AEs). Results: Of 15 pts (DL1: 4, DL2A: 3, DL2: 8), 11 continued on treatment at the time of the data cut. 14/15 pts experienced AEs; 3 experienced serious unrelated AEs (urinary tract infection, urosepsis, and large intestinal obstruction) all in DL1, 2 led to death; 10 experienced Grade >3 AEs and 2 experienced AEs of special interest, considered related to ERDA (Table). No DLTs were observed in any cohorts, 8 mg with UPT + CET was established as the RP2D. At data cut-off, investigator-assessed best overall response rate (CR+PR+uCR+uPR) in pts treated with the RP2D was 71% and disease control rate was 100% for RECIST 1.1 evaluable pts (n=7). Conclusions: 8 mg ERDA with UPT+240 mg CET was well tolerated and established as the RP2D. The combination of ERDA+CET is being further explored in the ongoing randomized phase 2 study in first-line cisplatin-ineligible mUC pts (NCT03473743). Clinical trial information: 2017-001980-19. [Table: see text]
- Published
- 2020
55. The SEMITEP trial: De-escalating chemotherapy in low-volume metastatic seminoma based on early FDG-PET
- Author
-
Brigitte Laguerre, Sylvain Ladoire, Serena Grimaldi, Yohann Loriot, Thierry Nguyen, Sophie Abadie Lacourtoisie, Stéphane Culine, Karim Fizazi, Philippe Barthélémy, Christophe Massard, Marine Gross-Goupil, Lionnel Geoffrois, Carole Helissey, Aude Flechon, Christine Chevreau, M. Texier, Emmanuelle Bompas, Hakim Mahammedi, and Gwenaelle Gravis
- Subjects
Cancer Research ,medicine.medical_specialty ,Chemotherapy ,business.industry ,medicine.medical_treatment ,Seminoma ,medicine.disease ,Low volume ,03 medical and health sciences ,0302 clinical medicine ,Oncology ,030220 oncology & carcinogenesis ,Metastatic seminoma ,Medicine ,Radiology ,business ,030215 immunology - Abstract
387 Background: A negative FDG-positron emission tomography/computerized tomography (PET) predicts the absence of viable seminoma cells after chemotherapy in men with metastatic seminoma. In this study, we assessed whether patients (pts) with low-volume metastatic seminoma can be treated with 2 cycles of etoposide-cisplatin (EP) followed by only one cycle of carboplatin (CARBO) on the basis of a negative interim PET, thereby limiting the burden of toxicity. Methods: In this non-randomised, multiple-center, phase 2 trial (NCT01887340), we enrolled pts with low-volume metastatic seminoma (with good prognosis according to IGCCCG and the Medical Research Council classifications). All pts with baseline PET-positive received EP for two cycles. After completion of first two cycles, pts underwent a second PET to assess response. Patients with a persistent positive PET (based on local review) proceeded directly to two additional EP cycles (for a total of 4); those who achieved a PET-negative received only one cycle of CARBO (AUC=7). The primary outcome was the proportion of pts who were PET-negative on interim PET and received de-escalating chemotherapy. Secondary endpoints include progression-free survival (PFS) and overall survival (OS). Results: Between June 2013 and July 2017, 102 pts were enrolled in the study. Three pts were deemed ineligible or not evaluable and thus 99 patients received treatment. After 2 first EP cycles, PET was available in 94 pts. Interim PET was negative in 68 pts (72%) and positive in 26 pts (28%). Overall, 63 pts (67.0%; 95% CI 57.5-76.5) were PET-negative and proceeded to one single cycle of CARBO. Overall, 24 (25.5%, 95% CI 17.1-34.9) patients had a PET positive after 2 EP and received 2 additional cycles of EP. After a median follow-up of 34.4 months, only 8 patients relapsed (2 in EP group and 6 in CARBO group). 2-year PFS rates were respectively 93.7% (95% CI 84.9-97.5) in the CARBO group and 92.9% (95% CI 77.4-98.0) in the EP group. Only one patient died during the 2 first cycles. Conclusions: De-escalating treatment based on a negative PET after 2 cycles of chemotherapy appears to be safe and feasible in the majority of patients with low-volume metastatic seminoma. Clinical trial information: NCT01887340.
- Published
- 2020
56. Nephrectomy after complete response to immune checkpoint inhibitors for metastatic renal cell carcinoma (mRCC): A new surgical challenge?
- Author
-
Jochen Walz, Karim Bensalah, Lionnel Geoffrois, V. Di Nunno, Louis Leblanc, Pierre Werle, Sylvain Ladoire, Gwenaelle Gravis, Géraldine Pignot, L. Balssa, Herve Lang, Antoine Thiery-Vuillemin, Laurence Albiges, and Philippe Barthélémy
- Subjects
Cancer Research ,business.industry ,Urology ,medicine.medical_treatment ,Immune checkpoint inhibitors ,lcsh:Diseases of the genitourinary system. Urology ,lcsh:RC870-923 ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,lcsh:RC254-282 ,Nephrectomy ,Oncology ,Renal cell carcinoma ,Cancer research ,Medicine ,business ,Complete response - Abstract
707 Background: In the current era of Immune checkpoint inhibitors (ICI), the role and timing of nephrectomy in the case of complete response on metastatic sites is still unknown. We aimed to evaluate the feasibility of nephrectomy for residual disease in patients with metastatic renal cell carcinoma (mRCC) and complete response (CR) on metastatic sites following ICI. Methods: Patients who underwent partial or radical nephrectomy after prior ICI between 2015 and 2018 were retrospectively included and clinicopathological data were reviewed. Perioperative data and postoperative outcomes were recorded. Results: Eleven patients without initial cytoreductive nephrectomy at diagnosis underwent delayed nephrectomy after long ICI administration because of complete response on metastatic sites. Median age was 59.8 years [38-67]. All patients had clear cell RCC on the initial biopsy. IMDC prognostic group was intermediate (81.8%) or poor (18.2%). ICI was administered as first-line therapy in 36.4% of cases (4/11) and as second-line option after TKI in 63.6% of cases (7/11). Treatments regimens were: nivolumab + ipilimumab (n = 3), nivolumab + tivozanib (n = 2) or nivolumab alone (n = 6). The median duration of ICI treatment was 10 months (range: 3-38 months) and the mean number of cycles was 27 (range: 6-75). Median operative time was 243 minutes [135-345] and mean blood loss was 909 cc [40-4000]. In 81.8% (n = 9) of the cases, surgeons experienced challenges for finding dissection planes due to inflammatory infiltration. The 30-day Clavien-Dindo postoperative complication rate was 54.6%, including 1 surgery-related death. Pathological report showed lymphocyte and/or macrophage infiltration in 54.6% and complete pathological response in 2 cases. Median follow-up was 15 months, with 73% of patients free from progression and 54% free from systemic treatment at 1 year. Conclusions: Nephrectomy following ICI for mRCC could allow achieving CR in selected patients. Due to technically complexity and complications rates, this surgery should be performed in centers with extensive experience.
- Published
- 2020
57. Accelerated BRAF mutation analysis using a fully automated PCR platform improves the management of patients with metastatic melanoma
- Author
-
Lionnel Geoffrois, Alexandre Harlé, Agnès Leroux, Julia Salleron, Pauline Gilson, Marie Husson, Jean-Louis Merlin, Delphine Serre, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Centre de Recherche en Automatique de Nancy (CRAN), and Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
0301 basic medicine ,Oncology ,medicine.medical_specialty ,Metastatic melanoma ,business.industry ,Operating procedures ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,therapeutic management ,BRAF ,3. Good health ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Fully automated ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Mutational status ,Personalized therapy ,business ,automated real-time PCR ,ComputingMilieux_MISCELLANEOUS ,Research Paper ,metastatic melanoma - Abstract
// Delphine Serre 1 , Julia Salleron 2 , Marie Husson 3 , Agnes Leroux 4 , Pauline Gilson 4 , Jean-Louis Merlin 4 , Lionnel Geoffrois 1 and Alexandre Harle 4 1 Institut de Cancerologie de Lorraine, Departement d’Oncologie Medicale, Vandoeuvre-les-Nancy Cedex 54519, France 2 Institut de Cancerologie de Lorraine, Cellule Data Biostatistiques, Vandoeuvre-les-Nancy Cedex 54519, France 3 Institut de Cancerologie de Lorraine, Biopathologie, Vandoeuvre-les-Nancy Cedex 54519, France 4 Universite de Lorraine, CNRS UMR 7039 CRAN, Institut de Cancerologie de Lorraine, Service de Biopathologie, Vandoeuvre-les-Nancy Cedex 54519, France Correspondence to: Alexandre Harle, email: a.harle@nancy.unicancer.fr Keywords: metastatic melanoma; BRAF; automated real-time PCR; therapeutic management Received: May 02, 2018 Accepted: July 31, 2018 Published: August 14, 2018 ABSTRACT Background: Determination of BRAF status is important for the therapeutic management of patients with metastatic melanoma. Objectives: We evaluated the impact of a faster determination of BRAF mutational status on the delay between initial consultation and initiation of treatment. Results: For the FA-PCR group a median delay of 16 days [11;18] was observed between initial consultation and the implementation of treatment, which was significantly lower than that observed for the SOP group (26 days [20;46], p = 0.035). Conclusions: In comparison to using conventional SOP, using an FA-PCR platform for BRAF mutation analysis of patients with metastatic melanoma significantly reduced the delay in initiation of personalized therapy by 10 days. Materials and Methods: Analysis of the BRAF mutation status of eight formalin-fixed paraffin-embedded (FFPE) tissue samples was performed using a CE-IVD fully-automated (FA) PCR-based platform. The delay between initial consultation and the implementation of treatment was compared between these samples (FA-PCR group) and a retrospective group of 29 FFPE samples analysed by standard operating procedures (SOP group) using conventional PCR.
- Published
- 2018
58. Sunitinib Alone or after Nephrectomy in Metastatic Renal-Cell Carcinoma
- Author
-
Christian Beisland, Jean-Christophe Bernhard, B. Laguerre, Stéphane Oudard, Marine Gross-Goupil, Alain Ravaud, Arnaud Mejean, Marc-Olivier Timsit, Lionnel Geoffrois, Claude Linassier, Frederic Rolland, Luc Cormier, Laurent Guy, Karim Bensalah, Jacques Hubert, Sandra Colas, Christine Theodore, Eric Lechevallier, Laurence Albiges, Simon Thezenas, Jean-Baptiste Beauval, Bernard Escudier, Thierry Lebret, Michael Aitchison, Jean-Jacques Patard, Herve Lang, Antoine Thiery-Vuillemin, Christine Chevreau, G. Gravis, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hôpital Saint-André, UNICANCER - Institut régional du Cancer Montpellier Val d'Aurelle (ICM), CRLCC Val d'Aurelle - Paul Lamarque, URC, hôpital Necker Enfants Maladies, Paris, CHU Pontchaillou [Rennes], Département d’Oncologie Médicale [Vandoeuvre Les Nancy], Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER-UNICANCER, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service d'Urologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Solvay Silica, Solvay (France), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), CHU Marseille, Hôpital Foch [Suresnes], Institut Claudius Regaud, Service de radiothérapie, CRLCC Eugène Marquis (CRLCC), Université libre de Bruxelles (ULB), Comité de Cancérologie (CCAFU), Association Française d'Urologie, Oncologie génito-urinaire, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), UNICANCER - Institut régional du Cancer [Montpellier] (ICM), Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), Développement et amélioration des plantes (UMR DAP), Centre National de la Recherche Scientifique (CNRS)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Recherche Agronomique (INRA)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), CRLCC Institut Claudius Regaud, Université Libre de Bruxelles [Bruxelles] (ULB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Adult ,Male ,medicine.medical_specialty ,Indoles ,Randomization ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,030232 urology & nephrology ,Urology ,Antineoplastic Agents ,urologic and male genital diseases ,Nephrectomy ,Risk Assessment ,law.invention ,03 medical and health sciences ,Postoperative Complications ,0302 clinical medicine ,Randomized controlled trial ,law ,Renal cell carcinoma ,Sunitinib ,medicine ,Carcinoma ,Humans ,Pyrroles ,Carcinoma, Renal Cell ,Aged ,Neoplasm Staging ,Aged, 80 and over ,business.industry ,Patient Selection ,Cancer ,General Medicine ,Middle Aged ,Prognosis ,medicine.disease ,Combined Modality Therapy ,Survival Analysis ,Kidney Neoplasms ,3. Good health ,Clinical trial ,030220 oncology & carcinogenesis ,Female ,business ,Follow-Up Studies ,medicine.drug - Abstract
International audience; BACKGROUND Cytoreductive nephrectomy has been the standard of care in metastatic renal-cell carcinoma for 20 years, supported by randomized trials and large, retrospective studies. However, the efficacy of targeted therapies has challenged this standard. We assessed the role of nephrectomy in patients with metastatic renal-cell carcinoma who were receiving targeted therapies. METHODS In this phase 3 trial, we randomly assigned, in a 1: 1 ratio, patients with confirmed metastatic clear-cell renal-cell carcinoma at presentation who were suitable candidates for nephrectomy to undergo nephrectomy and then receive sunitinib (standard therapy) or to receive sunitinib alone. Randomization was stratified according to prognostic risk (intermediate or poor) in the Memorial Sloan Kettering Cancer Center prognostic model. Patients received sunitinib at a dose of 50 mg daily in cycles of 28 days on and 14 days off every 6 weeks. The primary end point was overall survival. RESULTS A total of 450 patients were enrolled from September 2009 to September 2017. At this planned interim analysis, the median follow-up was 50.9 months, with 326 deaths observed. The results in the sunitinib-alone group were noninferior to those in the nephrectomy-sunitinib group with regard to overall survival (stratified hazard ratio for death, 0.89; 95% confidence interval, 0.71 to 1.10; upper boundary of the 95% confidence interval for noninferiority
- Published
- 2018
59. Physicians’ satisfaction with health-related quality of life (HRQoL) assessment in daily clinical practice using electronic patient-reported outcome (ePRO) for cancer patients
- Author
-
Philippe Barthélémy, Sophie Paget-Bailly, Stefano Kim, J.-C. Eymard, Amélie Anota, Antoine Thiery-Vuillemin, Hamadi Almotlak, Olivier Adotevi, Elsa Curtit, Virginie Westeel, Guillaume Mouillet, J. Fritzsch, N. Meneveau, O. Djoumakh, Tristan Maurina, Lionnel Geoffrois, Laura Mansi, Guillaume Eberst, and Marine Jary
- Subjects
0301 basic medicine ,Health related quality of life ,medicine.medical_specialty ,business.industry ,Hematology ,Electronic patient-reported outcome ,University hospital ,Clinical Practice ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,Patient Self-Report ,030220 oncology & carcinogenesis ,Family medicine ,Daily practice ,Visual accommodation ,medicine ,Clinical care ,business - Abstract
Background Routine Electronic Monitoring of HRQoL (REMOQOL) in daily clinical care with real-time feedback to physicians could help to manage treatment-related toxicities, to personalize supportive care, and to assess the treatment benefit from the patients’ point of view. Physicians’ satisfaction with REMOQOL was evaluated in two French clinical trials (CT) assessing its feasibility. Methods Physicians’ satisfaction was evaluated in two CT: QOLIBRY a monocentric CT for breast, lung and colorectal cancers, and QUANARIE a multicentric CT involving 8 centres of France for renal cancer. Patients were invited to complete before each visit the EORTC QLQ-C30 questionnaire, cancer site-specific modules and selected items related to treatments, using the CHES software on tablets and/or computers at the hospital or at home. During the visit, the physicians had real-time access to visual summaries of HRQoL scores evolution. Physicians’ satisfaction was evaluated with a questionnaire specifically designed for these CT. The questionnaire addressed 43 items and aimed to evaluate if REMOQOL was a useful tool for the physician and the usability of the CHES software. Results Between September 2016 and March 2019, 45 physicians included 249 patients (QOLIBRY n = 193, QUANARIE n = 56). Twenty-six (58%) physicians completed the survey. Among them, 18 (69%) looked at the HRQoL results. HRQoL results helped to better understand the patient’s medical condition for 11 (61%) of the physicians. Discussion about HRQoL results with the patient was easy (n = 15; 83%) and REMOQOL improved communication with patients (n = 8; 44%). Physicians declared that REMOQOL helped them to adapt patient’s management (n = 10; 56%) and to support supportive care prescription (n = 8; 44%) without extending the time of consultations (n = 12; 67%). Seventy-three per cent (n = 19) would agree to integrate REMOQOL for all patients in their daily practice. Conclusions Physicians used REMOQOL as a complementary tool and were globally satisfied. However, information about the objectives, trainings and recommendations for using HRQoL results in routine are essentials and must be enhanced to involve all the physicians. Clinical trial identification QOLIBRY: NCT02844608 QUANARIE: NCT03062410. Legal entity responsible for the study University Hospital of Besancon. Funding Novartis. Disclosure G. Mouillet: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Honoraria (self), Advisory / Consultancy: Sanofi; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self): Amgen; Honoraria (self): BMS; Honoraria (self): Roche; Honoraria (self), Travel / Accommodation / Expenses: Ipsen; Honoraria (self), Travel / Accommodation / Expenses: Astellas. A. Thiery-Vuillemin: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Sanofi; Honoraria (self), Honoraria (institution), Travel / Accommodation / Expenses: Janssen; Honoraria (self), Honoraria (institution): Novartis; Honoraria (self), Honoraria (institution): Ipsen; Honoraria (self), Honoraria (institution), Travel / Accommodation / Expenses: Roche/Genentech; Honoraria (self), Honoraria (institution), Travel / Accommodation / Expenses: BMS; Honoraria (self), Honoraria (institution), Travel / Accommodation / Expenses: MSD; Honoraria (self), Honoraria (institution): Astellas Pharma. E. Curtit: Honoraria (self): Roche; Honoraria (self): Novartis; Honoraria (self): Eisai; Honoraria (self): AstraZeneca; Honoraria (self): Pfizer. G. Eberst: Honoraria (self): MSD; Honoraria (self): BMS; Honoraria (self): Boeringher Ingelheim; Honoraria (self): Roche; Honoraria (self): AstraZeneca. P. Barthelemy: Advisory / Consultancy: Novartis; Advisory / Consultancy: BMS; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Roche; Advisory / Consultancy: MSD; Advisory / Consultancy: Janssen; Advisory / Consultancy: Sanofi; Honoraria (self): Astellas. L. Geoffrois: Travel / Accommodation / Expenses: Merck; Travel / Accommodation / Expenses: MSD; Travel / Accommodation / Expenses: BMS. A. Anota: Honoraria (self), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self): BMS; Honoraria (self): Roche. All other authors have declared no conflicts of interest.
- Published
- 2019
60. Tumeurs germinales primitives du médiastin : expérience de l’Institut de cancérologie de Lorraine sur une période de 20 ans (1990-2012)
- Author
-
Mathilde Deblock, Charlotte Joly, Lionnel Geoffrois, and Emmanuel Desandes
- Subjects
Gynecology ,Cancer Research ,medicine.medical_specialty ,Oncology ,business.industry ,Medicine ,Radiology, Nuclear Medicine and imaging ,Hematology ,General Medicine ,business - Abstract
Resume L’objectif de cette etude est de rapporter les resultats de la prise en charge de patients traites a l’Institut de cancerologie de Lorraine pour une tumeur germinale primitive du mediastin (TGM). Patients et methode Dix neuf patients traites pour une TGM entre le 1 er janvier 1990 et le 31 decembre 2012 ont ete inclus. Resultats Trois patients presentaient des seminomes mediastinaux et 16 des tumeurs germinales non seminomateuses. Tous les patients ont recu une chimiotherapie a base de cisplatine. La dose intensite moyenne du cisplatine etait de 33,48 mg/m 2 /semaine. A la fin de la chimiotherapie, trois patients (15,8 %) presentaient une reponse complete marqueurs negatifs (RCM-), sept (36,8 %) une reponse partielle marqueurs negatifs (RPM-), cinq (26,32 %) une reponse partielle marqueurs positifs (RPM+), trois (15,8 %) une maladie refractaire et un patient etait decede. En cas de rechute, celle-ci avait lieu dans les 13 mois. La survie globale a un et cinq ans etait respectivement de 78 et 36 % toutes histologies confondues et de 81 et 33 % dans le groupe des TGNS. La survie sans recidive a cinq ans etait de 43 % toutes histologies confondues et 38,5 % dans le groupe des TGNS. Conclusion Notre etude a permis de confirmer une prise en charge des TGM conforme aux donnees de la litterature.
- Published
- 2014
61. Biomarkers predict enhanced clinical outcomes with afatinib versus methotrexate in patients with second-line recurrent and/or metastatic head and neck cancer
- Author
-
Barbara Burtness, Ezra E.W. Cohen, Jérôme Fayette, Makoto Tahara, Jean-Pascal Machiels, Robert I. Haddad, Flavio Solca, Joël Guigay, Thomas Gauler, Nicholas F. Dupuis, Marco Merlano, X.J. Cong, Audrey Mailliez, Nicole C. Krämer, Lionnel Geoffrois, Juan J. Grau, E. Ehrnrooth, Lisa Licitra, Neil W. Gibson, Paul Clement, J. M. Del Campo, and Jan B. Vermorken
- Subjects
0301 basic medicine ,Oncology ,Antimetabolites ,Afatinib ,Biopsy ,Medizin ,afatinib ,Administration, Oral ,HNSCC ,0302 clinical medicine ,Neoplasm Metastasis ,Tissue microarray ,Tumor ,Hematology ,Antineoplastic ,Head and Neck Tumors ,Local ,Head and Neck Neoplasms ,030220 oncology & carcinogenesis ,Administration ,Carcinoma, Squamous Cell ,Biomarker (medicine) ,biomarker ,Administration, Intravenous ,Veristrat ,Intravenous ,medicine.drug ,Oral ,medicine.medical_specialty ,Antimetabolites, Antineoplastic ,EGFR ,Oncology and Carcinogenesis ,Disease-Free Survival ,methotrexate ,03 medical and health sciences ,Predictive Value of Tests ,Internal medicine ,medicine ,Biomarkers, Tumor ,Humans ,Progression-free survival ,Oncology & Carcinogenesis ,business.industry ,Squamous Cell Carcinoma of Head and Neck ,Head and neck cancer ,Carcinoma ,Original Articles ,medicine.disease ,Head and neck squamous-cell carcinoma ,phase III ,030104 developmental biology ,Neoplasm Recurrence ,Squamous Cell ,Quinazolines ,Methotrexate ,Human medicine ,Neoplasm Recurrence, Local ,business ,Biomarkers - Abstract
Background In the phase III LUX-Head & Neck 1 (LUX-H&N1) trial, second-line afatinib significantly improved progression-free survival (PFS) versus methotrexate in patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). Here, we evaluated association of prespecified biomarkers with efficacy outcomes in LUX-H&N1. Patients and methods Randomized patients with R/M HNSCC and progression following ≥2 cycles of platinum therapy received afatinib (40 mg/day) or methotrexate (40 mg/m2/week). Tumor/serum samples were collected at study entry for patients who volunteered for inclusion in biomarker analyses. Tumor biomarkers, including p16 (prespecified subgroup; all tumor subsites), EGFR, HER2, HER3, c-MET and PTEN, were assessed using tissue microarray cores and slides; serum protein was evaluated using the VeriStrat® test. Biomarkers were correlated with efficacy outcomes. Results Of 483 randomized patients, 326 (67%) were included in the biomarker analyses; baseline characteristics were consistent with the overall study population. Median PFS favored afatinib over methotrexate in patients with p16-negative [2.7 versus 1.6 months; HR 0.70 (95% CI 0.50–0.97)], EGFR-amplified [2.8 versus 1.5 months; HR 0.53 (0.33–0.85)], HER3-low [2.8 versus 1.8 months; HR 0.57 (0.37–0.88)], and PTEN-high [1.6 versus 1.4 months; HR 0.55 (0.29–1.05)] tumors. Afatinib also improved PFS in combined subsets of patients with p16-negative and EGFR-amplified tumors [2.7 versus 1.5 months; HR 0.47 (0.28–0.80)], and patients with p16-negative tumors who were EGFR therapy-naïve [4.0 versus 2.4 months; HR 0.55 (0.31–0.98)]. PFS was improved in afatinib-treated patients who were VeriStrat ‘Good’ versus ‘Poor’ [2.7 versus 1.5 months; HR 0.71 (0.49–0.94)], but no treatment interaction was observed. Afatinib improved tumor response versus methotrexate in all subsets analyzed except for those with p16-positive disease (n = 35). Conclusions Subgroups of HNSCC patients who may achieve increased benefit from afatinib were identified based on prespecified tumor biomarkers (p16-negative, EGFR-amplified, HER3-low, PTEN-high). Future studies are warranted to validate these findings. Clinical trial registration NCT01345682.
- Published
- 2017
62. [Advances in the management of cervical lymphadenopathies of unknown primary: advances in diagnostic imaging and surgical modalities and new international staging system]
- Author
-
Idriss, Troussier, Guillaume, Klausner, Sylvain, Morinière, Eivind, Blais, Jean-Christophe Faivre, Ambroise, Champion, Lionnel, Geoffrois, Carole, Pflumio, Emmanuel, Babin, Philippe, Maingon, and Juliette, Thariat
- Subjects
Biopsy, Fine-Needle ,Carcinoma ,Antineoplastic Agents ,Chemoradiotherapy ,Combined Modality Therapy ,Head and Neck Neoplasms ,Lymphatic Metastasis ,Carcinoma, Squamous Cell ,Humans ,Neoplasms, Unknown Primary ,Papillomaviridae ,Neck ,Neoplasm Staging ,Tonsillectomy - Abstract
Cervical lymphadenopathies of unknown primary represent 3 % of head and neck cancers. Their diagnostic work up has largely changed in recent years. This review provides an update on diagnostic developments and their potential therapeutic impact.This is a systematic review of the literature.In recent years, changes in epidemiology-based prognostic factors such as human papilloma virus (HPV) cancers, advances in imaging and minimally invasive surgery have been integrated in the management of cervical lymphadenopathies of unknown primary. In particular, systematic use of PET scanner and increasing practice of robotic or laser surgery have contributed to increasing detection rate of primary cancers. These allow more adapted and personalized treatments. The impact of changes in the eighth TNM staging system is discussed.The management of cervical lymphadenopathies of unknown primary cancer has changed significantly in the last 10 years. On the other hand, practice changes will have to be assessed.
- Published
- 2017
63. Combining gemcitabine, cisplatin, and ifosfamide (GIP) is active in patients with relapsed metastatic germ-cell tumors (GCT): a prospective multicenter GETUG phase II trial
- Author
-
Lionnel Geoffrois, Remy Delva, N. Houede, Frederic Rolland, Agnès Laplanche, J.-C. Eymard, B. Laguerre, Aude Flechon, Karim Fizazi, Stéphane Culine, D. Burcoveanu, G. Gravis, Christine Chevreau, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Léon Bérard [Lyon], Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), Institut Claudius Regaud, CRLCC Institut Claudius Regaud, CRLCC Eugène Marquis (CRLCC), Institut de cancérologie de l'Ouest - Paul Papin (ICO - Paul Papin), CRLCC Jean Godinot, CRLCC René Gauducheau, Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Institut Bergonié - CRLCC Bordeaux, Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1), Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Hôpital Saint-Louis, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut Bergonié [Bordeaux], Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)
- Subjects
Male ,Oncology ,030232 urology & nephrology ,Salvage therapy ,Kaplan-Meier Estimate ,Deoxycytidine ,Gastroenterology ,Testicular Neoplasms/*drug therapy/mortality/pathology ,0302 clinical medicine ,Neoplasms ,Antineoplastic Combined Chemotherapy Protocols ,Prospective Studies ,Ifosfamide ,Hematology ,Middle Aged ,Neoplasms, Germ Cell and Embryonal ,Ifosfamide/administration & dosage ,Chemotherapy regimen ,3. Good health ,Treatment Outcome ,Germ Cell and Embryonal/*drug therapy/mortality/secondary ,Lymphatic Metastasis ,030220 oncology & carcinogenesis ,medicine.drug ,Adult ,medicine.medical_specialty ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Drug Administration Schedule ,Young Adult ,03 medical and health sciences ,Testicular Neoplasms ,Internal medicine ,Deoxycytidine/administration & dosage/analogs & derivatives ,medicine ,Local/*drug therapy ,Humans ,Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ,Progression-free survival ,Survival rate ,Salvage Therapy ,business.industry ,medicine.disease ,Gemcitabine ,Regimen ,Neoplasm Recurrence ,Cisplatin ,Neoplasm Recurrence, Local ,business ,Cisplatin/administration & dosage ,Febrile neutropenia - Abstract
International audience; BACKGROUND: The standard treatment of patients with metastatic germ-cell tumor (GCT) relapsing after first-line chemotherapy is based on a cisplatin and ifosfamide-containing three-drug regimen, which usually yields a complete response (CR) rate \textless50%. As gemcitabine consistently displayed activity in patients with advanced GCT and as synergy with cisplatin was reported, we integrated this drug into the salvage triplet regimen and assessed its activity in this phase II study. PATIENTS AND METHODS: The GIP regimen consisted in gemcitabine 1000 mg/m(2) day 1 and 5, ifosfamide 1200 mg/m(2)/day day 1-5, cisplatin 20 mg/m(2)/day day 1-5, and granulocyte colony-stimulating factor 263 mug/day day 7-15, repeated every 3 weeks for four cycles. Eligibility criteria were that patients had favorable prognostic factors to conventional-dose salvage chemotherapy including a testis primary tumor and a previous CR to first-line chemotherapy for metastatic disease. The primary end point was the CR rate and a two-stage Simon design was used. RESULTS: Thirty-seven patients were accrued and 29 (78%) achieved a favorable response, including a CR in 20 (54%) and a partial response with normalization of tumor markers (PRm-) in 9 (24%). With a median follow-up of 53 months (13-81), the 2-year overall survival rate is 73% (57%-84%) and the continuous progression-free survival rate is 51% (35%-66%). Myelosuppression was the main toxicity including febrile neutropenia in 8 (22%) patients and 18 (50%) cases required platelet infusion. No grade 3 and 4 peripheral neurotoxicity or renal toxicity occurred. Two patients died of treatment-related toxicity, one of them with cancer progression. CONCLUSION: In a multicenter context, four cycles of the GIP regimen achieved a high CR rate in patients with relapsed testicular GCT. The GIP regimen avoided severe neurotoxicity and yielded a high survival rate. CLINICAL TRIAL NUMBER: NCT00127049.
- Published
- 2014
64. A Risk-adapted Study of Cisplatin and Etoposide, with or Without Ifosfamide, in Patients with Metastatic Seminoma: Results of the GETUG S99 Multicenter Prospective Study
- Author
-
A. Caty, Stéphane Culine, Rémi Delva, Agnès Laplanche, Frank Priou, Philippe Beuzeboc, Christine Chevreau, Frederic Rolland, Pierre Kerbrat, Lionnel Geoffrois, Jean-pierre Malhaire, Olivier Rixe, Karim Fizazi, and Marie-Stephanie Aubelle
- Subjects
Adult ,Male ,medicine.medical_specialty ,Time Factors ,Urology ,medicine.medical_treatment ,Kaplan-Meier Estimate ,Neutropenia ,Gastroenterology ,Disease-Free Survival ,Young Adult ,Testicular Neoplasms ,Risk Factors ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Granulocyte Colony-Stimulating Factor ,medicine ,Animals ,Humans ,Ifosfamide ,Prospective Studies ,Prospective cohort study ,Survival analysis ,Etoposide ,Aged ,Chemotherapy ,business.industry ,Seminoma ,Middle Aged ,medicine.disease ,Chemotherapy regimen ,Surgery ,Treatment Outcome ,France ,Cisplatin ,business ,medicine.drug - Abstract
Background Whether patients with good prognosis and intermediate/poor prognosis advanced seminoma should be treated differently has not been defined. Objective To assess a risk-adapted chemotherapy regimen in patients with advanced seminoma. Design, setting, and participants A total of 132 patients were included in this prospective study. Patients with a good prognosis according to the International Germ Cell Cancer Collaboration Group (IGGCCG) were treated with four cycles of cisplatin-etoposide (EP). Patients with an intermediate prognosis according to the IGCCCG (or a poor prognosis according to the Medical Research Council classification) were treated with four cycles of VIP (EP and ifosfamide) and granulocyte colony-stimulating factor (G-CSF). Outcome measurements and statistical analysis Survival curves were estimated using the Kaplan-Meier method. Results and limitations The median follow-up was 4.5 yr (range: 0.4–11.6 yr). Among 108 patients (82%) with a good prognosis who received EP, grade 3–4 toxicity included neutropenia (47%) and neutropenic fever (12%). Among the 24 patients (18%) with an intermediate/poor prognosis who received VIP plus G-CSF, toxicity included grade 3–4 neutropenia (36%), neutropenic fever (23%), thrombocytopenia (23%), anemia (23%), and a toxicity-related death ( n =1; 4%). The 3-yr progression-free survival (PFS) rate was 93% (range: 85–97%) in the good prognosis group and 83% (range: 63–93%) in the intermediate/poor prognosis group ( p =0.03 for PFS). The 3-yr overall survival (OS) rate was 99% (range: 92–100%) and 87% (range: 67–95%), respectively ( p Conclusions A risk-adapted chemotherapy policy for advanced seminoma yielded an excellent outcome with a 3-yr OS rate of 96%.
- Published
- 2014
65. Clinical Benefit of Everolimus as Second-Line Therapy in Metastatic Renal Cell Carcinoma: The French Retrospective SECTOR Study
- Author
-
Brigitte Laguerre, François Bidault, Florence Joly, Nadine Houédé, Nadia Kelkouli, Oliver Lucidarme, Bernard Escudier, Stéphane Oudard, Lionnel Geoffrois, K. Slimane, Marine Gross-Goupil, Yann Vano, Philippe Barthélémy, Service d'oncologie médicale [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Paris Descartes - Paris 5 (UPD5), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Cancers et préventions, Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Département d'oncologie médicale [Rennes], CRLCC Eugène Marquis (CRLCC), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Département d'Oncologie et Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), CHU Bordeaux [Bordeaux], Service de Radiologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), Novartis Pharma S.A.S., Oncologie génito-urinaire, Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], and Novartis France SAS
- Subjects
Male ,Oncology ,mTOR inhibitor ,Phases of clinical research ,Pharmacology ,[SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology ,chemistry.chemical_compound ,0302 clinical medicine ,Renal cell carcinoma ,Observational study ,Clinical endpoint ,030212 general & internal medicine ,Neoplasm Metastasis ,Aged, 80 and over ,Real-world study ,Middle Aged ,Kidney Neoplasms ,3. Good health ,Treatment Outcome ,030220 oncology & carcinogenesis ,Female ,France ,Nivolumab ,medicine.drug ,Adult ,medicine.medical_specialty ,Cabozantinib ,Urology ,Antineoplastic Agents ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Drug Administration Schedule ,03 medical and health sciences ,Internal medicine ,medicine ,Carcinoma ,Humans ,Everolimus ,Carcinoma, Renal Cell ,Aged ,Retrospective Studies ,VEGFR inhibitor ,business.industry ,Sequential targeted therapy ,medicine.disease ,Survival Analysis ,Confidence interval ,respiratory tract diseases ,chemistry ,business - Abstract
International audience; BACKGROUND:Real-world data of everolimus after vascular endothelial growth factor receptor (VEGFR)-tyrosine kinase inhibitor (TKI) therapy in metastatic renal cell carcinoma (mRCC) are limited.PATIENTS AND METHODS:The retrospective, noninterventional SECTOR (SECond line with afiniTOR) study (N = 165) assessed outcomes of second-line everolimus after initial VEGFR-TKI (TKI-everolimus, n = 144) and of third-line VEGFR-TKI after everolimus (TKI-everolimus-TKI, n = 59) in patients with mRCC. The primary end point was duration of everolimus therapy for both populations.RESULTS:Median duration was 4.0 months (range, 0.0-33.0 months) for second-line everolimus and 18.0 months (range, 2-78 months) for sequential VEGFR-TKI and everolimus. Median overall survival (OS) for this sequence was 36.0 months (95% confidence interval [CI], 27.0-56.0 months) and was longer for patients who received a first-line TKI for ≥ 9 months (not reached) than for < 9 months (28.0 months; P < .001). During second-line everolimus treatment, commonly reported adverse events (all grades) were fatigue (n = 66, 40.7%), anemia (n = 58, 35.8%), and stomatitis (n = 41, 25.3%). Median duration from initiation of first-line TKI to the end of the third-line TKI was 24.0 months (95% CI, 19.0-29.0 months). Median OS for this sequence was 41.0 months (95% CI, 25.0-57.0 months) and was significantly longer for patients who received the first-line TKI for ≥ 9 months (37.5 months) than for < 9 months (19.0 months; P < .0001).CONCLUSION:These results reflect clinical use of sequential TKI-everolimus and TKI-everolimus-TKI and provide additional evidence that everolimus could be an option in second-line therapy in mRCC. Results of the CheckMate-025 (Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma) and METEOR (Metastatic RCC Phase 3 Study Evaluating Cabozantinib versus Everolimus) studies might change the treatment landscape.
- Published
- 2016
66. Immune checkpoint inhibitors in a cohort of 206 metastatic uveal melanomas patients
- Author
-
Manuel Rodrigues, Nathalie Cassoux, Sophie Piperno-Neumann, Raymond L. Barnhill, L. Gastaud, Y. Le Corre, Vincent Servois, Thierry Lesimple, Pascale Mariani, Sophie Gardrat, Nicolas Penel, Sylvie Negrier, Mathilde Saint-Ghislain, Lionnel Geoffrois, and Jean-Emmanuel Kurtz
- Subjects
Oncology ,education.field_of_study ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Population ,Ipilimumab ,Hematology ,Pembrolizumab ,Immunotherapy ,medicine.disease ,Metastasis ,Internal medicine ,Cohort ,Medicine ,Progression-free survival ,Nivolumab ,education ,business ,medicine.drug - Abstract
Background Uveal melanomas (UM) are BRAF-wild type tumors associated with dismal prognosis for which no systemic therapy is active. We report our experience with immune checkpoint inhibitors (ICI) in metastatic UM patients. Methods Ambispective cohort of metastatic UM patients treated with ICI in eight French centers. Response rate, progression-free survival (PFS) and overall survival were retrieved. Results 206 evaluable patients started their first ICI treatment between December 2012 and January 2019. The population consisted of 98 men and 108 women. Median age was 57.5 yo (19; 82). Seventy-four patients had been enucleated, 131 had received proton beam therapy, one had received brachytherapy. The median time to first metastasis was 29.4 months (0-380.4). ICI were first prescribed in first-line in 68 patients, in second-line in 79 patients, in third-line or more in 80 patients. One hundred forty-four patients received pembrolizumab (63%), 58 nivolumab (25%) and 21 ipilimumab (9%). Metastatic sites at initiation of ICI were liver, lung, skin, and bone for 201, three, one and one patients, respectively. Liver was the sole metastatic site in 201 patients. Patients received a median number of four ICI infusions (1-60+). Treatment was suspended because of immune side effects in 21 patients. Nine objective responses were observed (four complete and five partial responses; 4.4%) including one patient with a hypermutated, MBD4-deficient tumor. Fifty-seven patients showed stable disease as best response (27.7%). Median PFS in the whole cohort was 4.1 months (0; 30.4) in 1st line, 4.9 months (0; 42,6) in 2nd line and 3.1 (1; 17.,3) months in 3rd line. Median PFS was 4.1 months in the ICI-resistant population and 27.4 months in the ICI-sensitive population (log-rank p-test Conclusions ICI are associated with a low response rate in UM but with longer PFS and a trend for longer overall survival in ICI-sensitive tumors. Immunotherapies should be investigated in this disease. ICI-sensitive cases are currently being explored to identify biomarkers of response. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.
- Published
- 2019
67. Impact of corticosteroids on nivolumab activity in metastatic clear cell renal cell carcinoma
- Author
-
B. Laguerre, C. Dalban, Philippe Barthélémy, P. Gillon, Marine Gross-Goupil, Sylvie Negrier, Laurence Albiges, S. Chabot, Stéphane Oudard, Mathieu Laramas, V. Sarradin, F. Tantot, Frank Priou, Bernard Escudier, C. Bolognini, Brice Chanez, M.J. de Vries, Sylvain Ladoire, Lionnel Geoffrois, and Félix Lefort
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Standard of care ,business.industry ,Pulmonary disease ,Hematology ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,Median time ,030220 oncology & carcinogenesis ,Family medicine ,Landmark analysis ,Overall survival ,medicine ,Corticosteroid use ,In patient ,Nivolumab ,business - Abstract
Background Nivolumab is a standard of care in patients (pts) with metastatic clear cell renal cell carcinoma (mccRCC) after failure of prior anti-angiogenic tyrosine-kinase inhibitors (TKIs). We evaluated the impact of corticosteroids (CS) during nivolumab in pts with mccRCC as part of a prospective clinical trial. Methods We conducted an ancillary study of the GETUG-AFU 26 NIVOREN study (NCT03013335), a multicenter prospective phase II safety study of nivolumab in mccRCC after progression on anti-angiogenic TKIs. Patients receiving CS at nivolumab initiation were excluded. Overall survival (OS) and progression free survival (PFS) of pts exposed to CS (≥ 10 mg of prednisone equivalents) or not during nivolumab were assessed. To overcome immortal time bias, we used two different landmark analysis methods. We first excluded pts who progressed or died before specified landmark timepoints (12 and 16 weeks). In a second method, patients treated with CS before landmark timepoints (12 and 16 and 24 weeks) were used to evaluate the effect of an early exposition to CS. Results Among the 665 evaluable pts, with a median follow up of 23.9 months, 113 (17 %) were exposed to CS during nivolumab, mainly to treat immune-related adverse events of any grade (74%). Other indications included infections (15%), complications of radiotherapy and chronic obstructive pulmonary disease. Median time to the first CS treatment was 21.6 weeks. Using a landmark at 12 weeks, OS rate at 12 months were 85.6% and 73.5% in pts exposed or not to CS [hazard ratio (HR), 0.57; p = 0.0017]. PFS rate at 12 months were 61.1% and 41.6% in pts exposed or not to CS (HR, 0.63; p = 0.0065). Landmark analyses at 16 weeks showed similar results. With the second landmark method, no differences in PFS or OS were observed between groups at 12 and 16 weeks. With a landmark set at 24 weeks, OS was similar in pts exposed or not to CS (HR, 1.14; p = 0.55). Conclusions The use of CS during nivolumab in mccRCC is not associated with a detrimental effect on survival outcomes. The positive association of corticosteroid use for irAEs with outcomes was not confirmed by second landmark modalities. Immortal time bias should be carefully considered when studying time-dependent variable. Clinical trial identification NCT03013335. Legal entity responsible for the study UNICANCER. Funding Bristol-Myers Squibb. Disclosure M. Gross-Goupil: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Ipsen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis. B. Laguerre: Honoraria (self), Travel / Accommodation / Expenses: BMS; Honoraria (self), Travel / Accommodation / Expenses: Pfizer; Honoraria (self): Novartis; Honoraria (self): Ipsen. P. Barthelemy: Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Ipsen; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Janssen-Cilag; Honoraria (self), Advisory / Consultancy: Sanofi. S. Negrier: Honoraria (self): Pfizer; Honoraria (self): Bms; Honoraria (self): Novartis; Honoraria (self): IPSEN; Honoraria (self): Euspharma. L. Geoffrois: Honoraria (self), Travel / Accommodation / Expenses: MSD; Honoraria (self), Travel / Accommodation / Expenses: BMS; Honoraria (self): Ipsen; Honoraria (self): Novartis; Travel / Accommodation / Expenses: Merck. S. Ladoire: Advisory / Consultancy, Travel / Accommodation / Expenses: BMS. M. Laramas: Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: SANOFI; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Speaker Bureau / Expert testimony: BMS; Speaker Bureau / Expert testimony: Amgen; Speaker Bureau / Expert testimony: IPSEN; Speaker Bureau / Expert testimony: Janssen; Travel / Accommodation / Expenses: Eisai. S. Oudard: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Ipsen. B. Escudier: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Roche; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Eusa; Advisory / Consultancy, Research grant / Funding (institution): Avevo; Advisory / Consultancy, Research grant / Funding (institution): Pfizer. L. Albiges: Advisory / Consultancy, Compensated to institution: Pfizer; Advisory / Consultancy, Compensated to institution: Novartis; Advisory / Consultancy, Compensated to institution: BMS; Advisory / Consultancy, Compensated to institution: Ipsen; Advisory / Consultancy, Compensated to institution: Roche; Advisory / Consultancy, Compensated to institution: MSD; Advisory / Consultancy, Compensated to institution: AstraZeneca. All other authors have declared no conflicts of interest.
- Published
- 2019
68. Expression of immune response biomarkers in head and neck squamous cell carcinoma (HNSCC) in irradiated area
- Author
-
C. Pflumio, Gilles Dolivet, Jean-Christophe Faivre, Julia Salleron, J. Thomas, Christian Borel, Xavier Sastre-Garau, and Lionnel Geoffrois
- Subjects
Oncology ,medicine.medical_specialty ,Stromal cell ,biology ,business.industry ,medicine.medical_treatment ,CD3 ,Hematology ,Immunotherapy ,medicine.disease ,Head and neck squamous-cell carcinoma ,Immune system ,Internal medicine ,medicine ,biology.protein ,Cytotoxic T cell ,Immunohistochemistry ,business ,CD8 - Abstract
Background HNSCC occurring in previously irradiated area have a poor prognosis. With immunotherapy, the inhibition of negative regulators of immune checkpoints programmed cell death ligand-1 (PD-L1) and CD8+ tumor-infiltrating lymphocytes (TILs) have been of greatest importance for antitumor immune response. Yet, the immune landscape of pretreated area remains poorly documented and should be investigated, especially since locoregional recurrences have recently been described as a predominant site of hyperprogression. We aimed to assess the tumoral microenvironment in terms of biomarkers for tumor immune response in irradiated area compared to de novo tumors. Methods This retrospective monocentric study analyzed 100 HNSCC tumor tissues from patients who had undergone surgery between January 2010 and November 2017. We compared the immune microenvironment in 50 de novo tumors and 50 tumor recurrence occurring within irradiated area. Formalin-fixed and paraffin embedded tumor tissue samples were reviewed by an experimented pathologist for immunohistochemistry. We assessed p16 status, CD3+ and CD8+ TILs and PD-L1 expression on tumor and immune cells, in stromal and intratumoral components. Results The density of CD3+ TILs was significantly lower, whether in intratumoral or stromal region within irradiated areas (p = 0.003 and p = 0.020 respectively). The expression of CD8+ TILs was not significantly different between the two cohorts. The percentage of tumor cells expressing PD-L1 TC (TPS=1%) was significantly lower in tumours developed within irradiated area than in de novo tumors (56.0% vs 86.0%) (p Conclusions There were persistence of cytotoxic cells and lower expression of PD-L1 and CD3+ TILs in tumors within irradiated area. This study provides first hypothesis to explain the fact that these lesions are less responsive to immunotherapy although they may still have antitumor capacity. The assessment of predictive biomarkers in patients treated by immunotherapy in randomized trials is required. Legal entity responsible for the study Dr Lionnel Geoffrois. Funding Has not received any funding. Disclosure C. Borel: Honoraria (self): Merck; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: BMS. L. Geoffrois: Honoraria (self), Travel / Accommodation / Expenses: MSD; Honoraria (self), Travel / Accommodation / Expenses: BMS; Honoraria (self): Ipsen; Honoraria (self): Novartis; Travel / Accommodation / Expenses: Merck Serono. All other authors have declared no conflicts of interest.
- Published
- 2019
69. Personalized treatment according to geriatric assessment in first-line recurrent and/or metastatic (R/M) head and neck squamous cell cancer (HNSCC) patients aged 70 or over: ELAN (ELderly heAd and Neck cancer) FIT and UNFIT trials
- Author
-
Cécile Ortholan, Philippe Debourdeau, C. Mertens, Cécile Michel, Y. Pointreau, H. Le Caer, Olivier Capitain, Laurence Bozec, Anne Auperin, Emmanuel Blot, J. Fayette, Frederic Rolland, Caroline Brard, Joël Guigay, Caroline Even, Dominique Schwob, Frederic Peyrade, Lionnel Geoffrois, Didier Cupissol, and Christian Sire
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Squamous cell cancer ,business.industry ,First line ,Head and neck cancer ,Geriatric assessment ,Hematology ,medicine.disease ,Clinical trial ,03 medical and health sciences ,Regimen ,030104 developmental biology ,0302 clinical medicine ,Oncology ,030220 oncology & carcinogenesis ,Internal medicine ,Relative risk ,medicine ,business ,Head and neck - Abstract
Background The main challenges in patients (pts) > = 70y are to cope with the treatment benefit/risk ratio and tumor related symptoms; no standard systemic treatment has been validated. With GERICO-GORTEC groups, we developed a large prospective clinical program named ELAN to improve the management of elderly HNSCC using an adapted geriatric evaluation feasible in daily practice and to set new standards of care for these pts. We report the results of ELAN FIT and UNFIT trials dedicated to elderly R/M HNSCC pts. Table: 1110O . ELAN-FIT trial ELAN-UNFIT trial N = 82 Carbo-5FU-cetux (n = 78) CX arm (n = 41) MTX arm (n = 41) Pts PS ECOG 0-1 (n = 47) (2 arms together) Pts PS ECOG 2 (n = 35) (2 arms together) Adverse events > =grade 4 24% 27% 22% 13% 40% Objective response rate At W12: 38% (central review) 12% 15% 13% 14% OS median (months) 14.7 (95%CI=11.0-18.2) 4.6 (95%CI=2.4-7.3) 4.6 (95%CI=2.3-7.7) 7.3 (95%CI=4.6-9.6) 2.1 (95%CI=1.5-3.2) 1-year OS rate 58% (95%CI=46%-68%) 22.5% (95% CI=12.3%-37.5%) 14.6% (95% CI=6.9%-28.4%) 27.7% (95% CI=16.9%-41.8%) 5.9% (95% CI=1.6%-19.1%) PFS median (months) 7.1 (95%CI=5.5-8.2) 2.4 (95%CI=1.5-3.8) 2.8 (95%CI=1.6-4.2) 3.8 (95%CI=2.6-5.5) 1.5 (95%CI=1.2-2.3) 1-year PFS rate 24.5% (95%CI=15.5%-34.6%) 7.5% (95% CI=2.6%-19.9%) 7.3% (95% CI=2.5%-19.4%) 12.8% (95% CI=6.0%-25.2%) 0% Methods To be included in one of the 2 trials, 1st line R/M SCCHN pts > = 70y must first be enrolled in ELAN-ONCOVAL study where they were classified as fit or unfit, using the ELAN geriatric evaluation (EGE). Comprehensive Geriatric Assessment was optional. Fit pts were proposed to be enrolled in the 2-stage phase II ELAN-FIT trial, which evaluated the cetuximab-carboplatin-5FU (EXTREME) combination in terms of efficacy (objective response at 12 weeks) and safety assessed by lack of grade > =4 toxicity and lack of loss of independence. Unfit pts were proposed to be enrolled in the randomized phase III ELAN-UNFIT trial, that compared 2 monotherapies, cetuximab (Cx) 500 mg/m² every 2 weeks versus weekly methotrexate (MTX) 40 mg/m² in terms of failure free survival (failures are progression, treatment stop, loss > = 2 points in Activities in Daily Living scale or death). Results 160 pts were enrolled in the trials. The UNFIT trial was stopped after futility analysis. Main results are shown in the table. Conclusions Fit elderly pts as selected using EGE, benefited from carboplatin based EXTREME regimen, with promising overall survival (OS), which compares favourably with that of younger pts. For unfit elderly pts, there was no efficacy difference of Cx and MTX. PS ECOG 2 pts did not benefit from systemic treatment. New therapeutic options should be explored for ECOG 0-1 unfit elderly pts. Clinical trial identification ELAN-UNFIT: NCT01884623 ELAN-FIT: NCT01864772. Legal entity responsible for the study Gustave Roussy and GORTEC. Funding INCA PAIR, Merck, Sandoz, GEMLUC-GEFLUC. Disclosure J. Guigay: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Advisory / Consultancy: Innate Pharma; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck. C. Even: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy: Innate Pharma. L. Geoffrois: Honoraria (self), Travel / Accommodation / Expenses: BMS; Honoraria (self), Travel / Accommodation / Expenses: MSD; Honoraria (self): Ipsen; Honoraria (self): Novartis; Travel / Accommodation / Expenses: Merck Serono. C. Sire: Travel / Accommodation / Expenses: Merck. J. Fayette: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy: Innate; Honoraria (self), Advisory / Consultancy: Biogen. F. Peyrade: Advisory / Consultancy: MSD; Advisory / Consultancy: Merck. P. Debourdeau: Non-remunerated activity/ies: Pfizer; Honoraria (self): Leo Pharma; Honoraria (self): Bayer. Y. Pointreau: Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy: MSD. All other authors have declared no conflicts of interest.
- Published
- 2019
70. NISCAHN: A phase II, multicenter nonrandomized trial aiming at evaluating nivolumab (N) in two cohorts of patients (pts) with recurrent/metastatic (R/M) salivary gland carcinoma of the head and neck (SGCHN), on behalf of the Unicancer Head & Neck Group
- Author
-
Laurence Digue, Frederic Rolland, Aurélie Guyennon, Sylvie Zanetta, Jérôme Fayette, Didier Cupissol, Christophe Le Tourneau, Jessy Delaye, Isabelle Jallut, Audrey Lardy-Cleaud, Laurence Bozec Lemoal, Valérie Costes, Sophie Couchon-Thaunat, Joël Guigay, Sylvie Chabaud, Anne-Françoise Dillies, Christian Borel, Caroline Even, and Lionnel Geoffrois
- Subjects
Cancer Research ,medicine.medical_specialty ,business.industry ,Adenoid cystic carcinoma ,Urology ,Head neck ,medicine.disease ,Salivary gland carcinoma ,stomatognathic diseases ,03 medical and health sciences ,0302 clinical medicine ,Oncology ,030220 oncology & carcinogenesis ,medicine ,Nivolumab ,business ,Head and neck ,030215 immunology - Abstract
6083 Background: SGCHN are rare tumors including adenoid cystic carcinoma (ACC) and non-ACC, with no standard systemic treatment for R/M pts. We evaluated N monotherapy in R/M SGCHN pts. Methods: R/M SGCHN pts (ACC or non-ACC) not eligible to local treatment and with centrally confirmed RECIST 1.1 disease progression over the last 6 months were enrolled and received N 3 mg/kg IV, every 2 weeks for a maximum of 12 months (mo). Possibility was given to re-start N in case of progression during the 2-year follow-up phase. Primary endpoint was 6-mo non-progression Rate (NPR6m) as per RECIST 1.1. Secondary endpoints included ORR, PFS, OS, and safety. Considering that N would be uninteresting if NPR6m ≤ 20% and promising if ≥ 40% and using a Fleming’s single-stage design (α: 5% unilateral, power: 90%), at least 14 successes/42 evaluable pts were required for each cohort to be positive. Results: 46 ACC and 52 Non-ACC pts (median age 61 yrs (range 29-81), 43.9% female, 55.1% PS1 and 2.0% PS2) were enrolled and received at least one dose of N. Median treatment duration was 5.5 mo (ACC) and 3.3 (Non-ACC). Median FU was 10.8 mo (ACC) and 8.3 mo (Non-ACC). 95 patients were evaluable for the primary endpoint. NPR6m was 15/45 pts (33.3%, 90%CI :21.8;46.6) and 7/50 pts (14.0%, 90%CI:6.8;24.7) for ACC and non-ACC pts respectively. 4 (8.7%) partial responses (PR) and 26 (56.5%) stable diseases (SD) were observed in ACC cohort while 2 (3.8%) PR and 22 (42.3%) SD were observed in non-ACC. Median PFS was 4.9 mo (95%CI = 3.4;5.6) in ACC pts and 1.8 mo (95%CI = 1.7;3.5) in non-ACC pts. The most common related adverse events (AE) ( > 10% by cohort) were asthenia, hyperthyroidism, diarrhea, rash, pruritus and hypothyroidism. 7/98 pts (7.1%) presented at least one related AE Grade 3-4 (mainly hepatic) and 9 pts (9.2%) prematurely discontinued Nivolumab due to toxicity. Conclusions: Limited efficacy was observed with N in R/M SGCHN pts. N in combination might be of interest and deserves exploration in ACC pts. Clinical trial information: NCT03132038.
- Published
- 2019
71. Cytoreductive nephrectomy (CN) in metastatic renal cancer (mRCC): Update on Carmena trial with focus on intermediate IMDC-risk population
- Author
-
Claude Linassier, Frederic Rolland, Luc Cormier, Arnaud Mejean, Alain Ravaud, Thierry Lebret, Marc-Olivier Timsit, Laurent Guy, Karim Bensalah, Laurence Albiges, Gwenaelle Gravis, Christine Chevreau, Bernard Escudier, Jean-Marc Tréluyer, Lionnel Geoffrois, Sandra Colas, Herve Lang, Simon Thezenas, Antoine Thiery-Vuillemin, and Stéphane Oudard
- Subjects
Oncology ,Cancer Research ,education.field_of_study ,medicine.medical_specialty ,Sunitinib ,business.industry ,Metastatic renal cancer ,Population ,03 medical and health sciences ,0302 clinical medicine ,Risk groups ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Cytoreductive nephrectomy ,business ,education ,030215 immunology ,medicine.drug - Abstract
4508 Background: Carmena was a randomized phase III trial, testing the benefit of CN followed by sunitinib (arm A) vs sunitinib alone (arm B), with stratification by MSKCC risk groups in 450 mRCC patients. Based on this trial, CN is not anymore recommended in mRCC (NEJM, Mejean et al, 2018). However there are questions about which patients could still benefit from CN, especially in intermediate risk group. In the present study, we investigated different subgroups from the Carmena trial to answer these questions. Methods: Carmena trial was initially stratified according to MSKCC risk groups. For the purpose of this analysis, we reclassified the patients based on IMDC risk groups. We also analyzed patients with one metastatic site vs more than one, as well as patients with secondary nephrectomy in arm B. Overall survival (OS) was the primary endpoint. Results: With a updated median FU of 61.5 months (mo), the median OS by ITT analysis was 15.6 vs 19.8 mo in arm A and B respectively stratified on MSKCC (HR 0.933 ; 95% CI [0.76- 1.15]) / stratified on IMDC (HR 0.957 ; 95% CI [0.78- 1.18]). Using IMDC risk group factors, 58.6% patients were intermediate and 41.4 % were poor risk. When looking at intermediate risk group only, 48.1% had only one risk factor (interval between diagnosis and treatment < 1y), with a median OS of 30.5 and 25.2 mo in arm A and B respectively (HR 1.24 [0.81 – 1.90]). By contrast, 51.9 % had two risk factors (mostly low hemoglobin, high corrected calcium or neutrophils), with a median OS of 16.6 and 31.2 mo in arm A and B respectively (HR 0.61 [0.41 – 0.91] p = 0.015). Regarding number of metastatic sites, 33% had only one metastatic site. Median OS was 23.6 and 22.7 mo in arm A and B respectively (HR 1.08 [0.75 – 1.57]. Finally, 40 patients had a secondary nephrectomy in arm B, with median OS of 48.5 mo [CI 95%: 27.9-64.4] vs 15.7 mo [CI 95%: 13.3-20.5] in patients who never had surgery. Conclusions: With longer FU, Carmena trial confirms that CN is not superior to sunitinib alone in ITT population, both with MSKCC and IMDC risk groups. However for patients with only one IMDC risk factor, CN might be beneficial. Number of metastatic site is not helpful to define good candidates for surgery. Finally, patients with secondary nephrectomy have very long OS, supporting this strategy. Clinical trial information: NCT00930033.
- Published
- 2019
72. Are immune checkpoint inhibitors (ICI) a valid option for papillary renal cell carcinoma (pRCC)? A multicenter retrospective study
- Author
-
Marine Gross-Goupil, Laurence Albiges, Alain Ravaud, Olivier Huillard, Philippe Barthélémy, Antoine Thiery-Vuillemin, Christine Chevreau, Sylvie Negrier, Elouen Boughalem, Carolina Saldana, Delphine Borchiellini, Manon de Vries-Brilland, Gwenaelle Gravis, Sylvain Ladoire, Bernard Escudier, Constance Thibault, Lionnel Geoffrois, Valérie Seegers, and Benoit Beuselinck
- Subjects
Cancer Research ,Papillary renal cell carcinomas ,business.industry ,Immune checkpoint inhibitors ,Cell ,Retrospective cohort study ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,Medicine ,business ,030215 immunology - Abstract
582 Background: pRCC is the most common non-clear cell RCC (nccRCC) and represents up to 15% of RCC. Pivotal studies evaluating ICI mostly excluded nccRCC. Therefore the efficacy of ICI in pRCC remains to be demonstrated. Methods: We retrospectively investigated the activity and safety of PD-1/PD-L1 inhibitors (PD-1i) specifically in patients (pts) with metastatic pRCC from 15 centers in France and Belgium. Pts baseline characteristics, treatment outcome and safety were collected. Primary endpoint was time-to-treatment failure (TTF). Secondary endpoints included objective response rate (ORR), overall survival (OS) and treatment-related adverse events (TRAEs). Results: From 02/2016 to 09/2018, 50 pRCC pts treated with PD-1i were included. Median age was 63 years (range: 27-84), 36 (72%) were male. Histology included 14 (28%) type 1 pRCC, 30 (60%) type 2 pRCC, 6 (12%) unclassified pRCC. PD-1i was used in first line setting in 5 pts (10%), in second line in 29 pts (58%) and in third line or beyond in 16 pts (32%). IMDC risk group at PD-1i start was 22% good, 44% intermediate and 33% poor. ICI used were PD-1 inhibitors in 47 pts (94%) and PD-L1 inhibitors in 3 pts (6%). PD-1 in was used as monotherapy in 94% of pts. With a median follow up of 10.7 months (95% Confidence Interval (CI): 6.8-14.8), the median TTF was 3.7 months (95% CI: 3.1, 10.1). In type 1, the median TTF was 7.1 months (95% CI: 3.2-NA) and 3.2 months (95% CI: 2.9-NA) in type 2. Median treatment duration was 3.2 months (range: 0.4-24.5, IQR: 2.4-6.4). Among the 45 pts evaluable for ORR, best response was complete response/partial response in 8 pts (16%), stable disease in 13 pts (26%) and progressive disease in 24 pts (48%). ORR was 25% in type 1 pRCC and 15% in type 2 pRCC. Median OS was 17.6 months (95% CI 11.4- not reached). TRAEs of grade 3-4 were noted in 6 patients (12%) which led to treatment discontinuation, no grade 5 were observed. Conclusions: This retrospective study is the largest cohort of metastatic pRCC treated with PD-1i to date. PD-1i exhibit limited activity in this pRCC population, with better TTF and ORR in type 1 pRCC. Our findings underline the need for further prospective clinical trials evaluating ICI combinations in pts with pRCC.
- Published
- 2019
73. Clinical activity of sunitinib rechallenge in metastatic renal cell carcinoma-Results of the REchallenge with SUnitinib in MEtastatic RCC (RESUME) Study
- Author
-
Mathieu Laramas, P. Gimel, Lionnel Geoffrois, Frederic Rolland, Brigitte Laguerre, Eric Legouffe, Sabrina Falkowski, Marjorie Baciuchka, Eric Yaovi Amela, Jean-Laurent Deville, Aline Guillot, Christian Pfister, Marine Gross-Goupil, Christine Chevreau, Helen Boyle, Delphine Topart, Stéphane Oudard, Gwénaël Denechere, and Sophie Abadie-Lacourtoisie
- Subjects
0301 basic medicine ,Oncology ,Adult ,Male ,Vascular Endothelial Growth Factor A ,Cancer Research ,medicine.medical_specialty ,Indoles ,medicine.medical_treatment ,Antineoplastic Agents ,urologic and male genital diseases ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Renal cell carcinoma ,Internal medicine ,medicine ,Sunitinib ,Humans ,In patient ,Pyrroles ,Adverse effect ,Objective response ,Carcinoma, Renal Cell ,Aged ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Middle Aged ,medicine.disease ,female genital diseases and pregnancy complications ,Nephrectomy ,Kidney Neoplasms ,030104 developmental biology ,Tolerability ,030220 oncology & carcinogenesis ,Retreatment ,Disease characteristics ,France ,business ,medicine.drug - Abstract
Aim To assess the efficacy and tolerability of sunitinib rechallenge in the third-line or later setting in patients with metastatic renal cell carcinoma (mRCC). Patients and methods This observational study comprised 61 mRCC patients at 19 centres in France who received sunitinib rechallenge between January 2006 and May 2013. Patients received first-line sunitinib, ≥1 different targeted therapies, and then sunitinib rechallenge. Patient/disease characteristics, tolerability, treatment modalities, and outcomes of therapeutic lines were recorded. The primary end-point was progression-free survival (PFS) in sunitinib rechallenge. Results Analyses included 52 patients; median age was 59 years, 75% were male, and 98% had clear-cell mRCC and prior nephrectomy. At sunitinib rechallenge versus first-line, patients had poorer performance (Karnofsky performance status 90–100: 30% versus 81%) and Memorial Sloan Kettering Cancer Centre prognostic risk (poor risk: 18% versus 3%). Overall, 20%, 65%, 12%, and 4% received sunitinib rechallenge as third-, fourth-, fifth-, and sixth-line therapy, respectively, at 14.6 months (median) after stopping initial treatment. With first-line sunitinib and rechallenge, median PFS was 18.4 and 7.9 months, respectively; objective response rate was 54% and 15%. Two of eight rechallenge responders had not achieved first-line response. Median overall survival was 55.9 months. The sunitinib rechallenge safety profile was as expected, with no new adverse events reported. Conclusions Sunitinib rechallenge is a feasible treatment option with potential clinical benefit for mRCC patients. Disease progression with first-line sunitinib may not be associated with complete or irreversible resistance to therapy.
- Published
- 2016
74. PD-029: Causes-of-death underestimate the burden of head and neck cancers in France (EPICORL study)
- Author
-
Y. Pointreau, L. Sagaon Teyssier, M. Bec, L. Lévy-Bachelot, Stéphane Temam, Lionnel Geoffrois, Michaël Schwarzinger, C. Godard, Florence Huguet, and Caroline Even
- Subjects
medicine.medical_specialty ,Oncology ,business.industry ,medicine ,Radiology, Nuclear Medicine and imaging ,Hematology ,Head and neck ,business ,Surgery - Published
- 2017
75. Temsirolimus and bevacizumab, or sunitinib, or interferon alfa and bevacizumab for patients with advanced renal cell carcinoma (TORAVA): a randomised phase 2 trial
- Author
-
Celine Ferlay, David Pérol, Emmanuel Sevin, Eric Legouffe, Ellen Blanc, Gwenaelle Gravis, Frederic Rolland, Brigitte Laguerre, Sylvie Negrier, Christine Chevreau, Remy Delva, Lionnel Geoffrois, Jacques-Olivier Bay, and Bernard Escudier
- Subjects
Adult ,Male ,medicine.medical_specialty ,Indoles ,Bevacizumab ,Phases of clinical research ,Antineoplastic Agents ,Antibodies, Monoclonal, Humanized ,Gastroenterology ,Disease-Free Survival ,Group B ,law.invention ,Randomized controlled trial ,law ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Sunitinib ,medicine ,Humans ,Pyrroles ,Carcinoma, Renal Cell ,Interferon alfa ,Aged ,Neoplasm Staging ,Aged, 80 and over ,Sirolimus ,Intention-to-treat analysis ,business.industry ,Antibodies, Monoclonal ,Interferon-alpha ,Middle Aged ,Temsirolimus ,Surgery ,Oncology ,Female ,business ,medicine.drug - Abstract
Summary Background Combining targeted treatments for renal cell carcinoma has been suggested as a possible method to improve treatment efficacy. We aimed to assess the potential synergistic or additive effect of the combination of bevacizumab, directed against the VEGF receptor, and temsirolimus, an mTOR inhibitor, in metastatic renal cell carcinoma. Methods TORAVA was an open-label, multicentre randomised phase 2 study undertaken in 24 centres in France. Patients aged 18 years or older who had untreated metastatic renal cell carcinoma were randomly assigned (2:1:1) to receive the combination of bevacizumab (10 mg/kg every 2 weeks) and temsirolimus (25 mg weekly; group A), or one of the standard treatments: sunitinib (50 mg/day for 4 weeks followed by 2 weeks off; group B), or the combination of interferon alfa (9 mIU three times per week) and bevacizumab (10 mg/kg every 2 weeks; group C). Randomisation was done centrally and independently from other study procedures with computer-generated permuted blocks of four and eight patients stratified by participating centre and Eastern Cooperative Oncology Group performance status. The primary endpoint was progression-free survival (PFS) at 48 weeks (four follow-up CT scans), which was expected to be above 50% in group A. Analysis was by intention to treat. The study is ongoing for long-term overall survival. This study is registered with ClinicalTrials.gov, number NCT00619268. Findings Between March 3, 2008 and May 6, 2009, 171 patients were randomly assigned: 88 to the experimental group (group A), 42 to group B, and 41 to group C. PFS at 48 weeks was 29·5% (26 of 88 patients, 95% CI 20·0–39·1) in group A, 35·7% (15 of 42, 21·2–50·2) in group B, and 61·0% (25 of 41, 46·0–75·9) in group C. Median PFS was 8·2 months (95% CI 7·0–9·6) in group A, 8·2 months (5·5–11·7) in group B, and 16·8 months (6·0–26·0) in group C. 45 (51%) of 88 patients in group A stopped treatment for reasons other than progression compared with five (12%) of 42 in group B and 15 (38%) of 40 in group C. Grade 3 or worse adverse events were reported in 68 (77%) of 88 patients in group A versus 25 (60%) of 42 in group B and 28 (70%) of 40 in group C. Serious adverse events were reported in 39 (44%) of 88, 13 (31%) of 42, and 18 (45%) of 40 patients in groups A, B, and C, respectively. Interpretation The toxicity of the temsirolimus and bevacizumab combination was much higher than anticipated and limited treatment continuation over time. Clinical activity was low compared with the benefit expected from sequential use of each targeted therapy. This combination cannot be recommended for first-line treatment in patients with metastatic renal cell carcinoma. Funding French Ministry of Health and Wyeth Pharmaceuticals.
- Published
- 2011
76. Management of Patients with Head and Neck Tumours Presenting at Diagnosis with a Synchronous Second Cancer at Another Anatomic Site
- Author
-
Benjamin Schipman, Marie-Christine Kaminsky, Hinda Mecellem, Didier Peiffert, Sophie Cortese, Lionnel Geoffrois, Emmanuel Desandes, Bruno Toussaint, Pierre Graff, Frédéric Marchal, Centre Alexis Vautrin (CAV), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre de Recherche en Automatique de Nancy (CRAN), and Université Henri Poincaré - Nancy 1 (UHP)-Institut National Polytechnique de Lorraine (INPL)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
medicine.medical_specialty ,medicine.medical_treatment ,Antineoplastic Agents ,Anatomic Site ,Kaplan-Meier Estimate ,Disease ,survival analysis ,Neoplasms, Multiple Primary ,03 medical and health sciences ,0302 clinical medicine ,Humans ,Medicine ,Radiology, Nuclear Medicine and imaging ,Head and neck ,Survival analysis ,Neoplasm Staging ,Retrospective Studies ,2. Zero hunger ,Chemotherapy ,Lung ,Radiotherapy ,business.industry ,Second cancer ,Middle Aged ,Combined Modality Therapy ,3. Good health ,Surgery ,[SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics ,synchronous neoplasms ,Treatment Outcome ,medicine.anatomical_structure ,Oncology ,Head and Neck Neoplasms ,030220 oncology & carcinogenesis ,Carcinoma, Squamous Cell ,multiple primary tumours ,Underweight ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
Aims To understand management strategies and outcomes of patients diagnosed with a head and neck tumour and a synchronous second cancer developed at another anatomic site. Materials and methods Retrospective analysis of all patients diagnosed with a head and neck carcinoma and a synchronous cancer and engaged in curative-intent treatments. To evaluate therapeutic strategies, each patient's treatment process was divided into sequential therapeutic modalities and corresponding targets (head and neck and/or synchronous tumour) were identified. Patient outcome was analysed with an intent-to-treat approach. Results : Forty-three patients were entered into the study (mean age=57.4 years). Synchronous tumours concerned the lung (57.8%), oesophagus (31.1%) or other sites (11.1%). Treatments were complex, including one to four consecutive modalities, with a mean duration of 4.6 months. When both tumours were advanced, treatments were frequently initiated with dual-spectrum chemotherapy (66.7%). In other situations, a locoregional treatment was often (81.1%) proposed immediately. When both tumours were in early stages, this initial locoregional treatment could be extended to target both tumours together (30.0%). For patients whose tumours differed in severity, this locoregional treatment targeted only one tumour (85%); priority was given to the most advanced one (76.5%). Nine patients had definitive treatment interruption. Associated risk factors were a low body mass index ( P =0.03) and advanced-stage tumours ( P =0.01). Thirty-one patients died (72.1%) with a median time to death of 7.7 months. The median follow-up for survivors was 46.2 months. Three-year overall survival was 33.9%. Low body mass index ( P =0.001), advanced-stage synchronous tumours ( P =0.03) and oesophageal primaries ( P =0.03) altered the overall survival. Three-year locoregional and metastatic progression-free survival was 40.8 and 62.5%, respectively. Low body mass index ( P =0.01) and advanced-stage synchronous tumours ( P =0.01) increased the risk of disease failure. Conclusions Head and neck tumours diagnosed with a synchronous cancer are a complex challenge. Despite a severe prognosis, patients who are not underweight, presenting with lower-stage tumours (especially the synchronous tumour) and without oesophageal involvement could most benefit from aggressive treatments.
- Published
- 2011
77. Quality of Life Assessment After Concurrent Chemoradiation for Invasive Bladder Cancer: Results of a Multicenter Prospective Study (GETUG 97-015)
- Author
-
Jean-Léon Lagrange, Jean-Marc Bachaud, Florence Joly, Véronique Beckendorf, Jean-Marc Ferrero, Caroline Bascoul-Mollevi, Andrew Kramar, Bruno Chauvet, Lionnel Geoffrois, Christine Chevreau, and Nedjila Allouache
- Subjects
Adult ,Male ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Urinary system ,Urinary Bladder ,Cystectomy ,Quality of life ,Surveys and Questionnaires ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Neoplasm Invasiveness ,Radiology, Nuclear Medicine and imaging ,Prospective Studies ,Prospective cohort study ,Aged ,Neoplasm Staging ,Carcinoma, Transitional Cell ,Radiation ,Bladder cancer ,Urinary bladder ,business.industry ,Radiotherapy Dosage ,Organ Preservation ,Middle Aged ,medicine.disease ,Combined Modality Therapy ,Surgery ,Radiation therapy ,medicine.anatomical_structure ,Urinary Bladder Neoplasms ,Oncology ,Quality of Life ,Female ,Fluorouracil ,Cisplatin ,business ,Chemoradiotherapy - Abstract
Purpose To evaluate bladder preservation and functional quality after concurrent chemoradiotherapy for muscle-invasive cancer in 53 patients included in a Phase II trial. Patient and Methods Pelvic irradiation delivered 45Gy, followed by an 18-Gy boost. Concurrent chemotherapy with cisplatin and 5-fluorouracil by continuous infusion was performed at Weeks 1, 4, and 7 during radiotherapy. Patients initially suitable for surgery were evaluated with macroscopically complete transurethral resection after 45Gy, followed by radical cystectomy in case of incomplete response. The European Organization for Research and Treatment of Cancer quality of life questionnaire QLQ-C30, specific items on bladder function, and the Late Effects in Normal Tissues–Subjective, Objective, Management, and Analytic (LENT-SOMA) symptoms scale were used to evaluate quality of life before treatment and 6, 12, 24, and 36 months after treatment. Results Median age was 68 years for 51 evaluable patients. Thirty-two percent of patients had T2a tumors, 46% T2b, 16% T3, and 6% T4. A visibly complete transurethral resection was possible in 66%. Median follow-up was 8 years. Bladder was preserved in 67% (95% confidence interval, 52–79%) of patients. Overall survival was 36% (95% confidence interval, 23–49%) at 8 years for all patients, and 45% (28–61%) for the 36 patients suitable for surgery. Satisfactory bladder function, according to LENT-SOMA, was reported for 100% of patients with preserved bladder and locally controlled disease 6–36 months after the beginning of treatment. Satisfactory bladder function was reported for 35% of patients before treatment and for 43%, 57%, and 29%, respectively, at 6, 18, and 36 months. Conclusions Concurrent chemoradiation therapy allowed bladder preservation with tumor control for 67% patients at 8 years. Quality of life and quality of bladder function were satisfactory for 67% of patients.
- Published
- 2011
78. Brain metastases response to nivolumab in patients with renal cell carcinoma (RCC): Prospective analysis from the GETUG-AFU 26 (NIVOREN) trial
- Author
-
Bernard Escudier, Sylvie Negrier, G. Gravis, Hakim Mahammedi, C. Dalban, Ronan Flippot, Florence Joly, Laurence Albiges, B. Laguerre, Christine Chevreau, F. Tantot, D. Borchiellini, Sylvain Ladoire, and Lionnel Geoffrois
- Subjects
Oncology ,medicine.medical_specialty ,business.industry ,Hematology ,medicine.disease ,03 medical and health sciences ,Prospective analysis ,0302 clinical medicine ,Renal cell carcinoma ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,In patient ,Nivolumab ,business ,030217 neurology & neurosurgery - Published
- 2018
79. Efficacy and safety of axitinib in metastatic papillary renal carcinoma (mPRC): Results of a GETUG multicenter phase II trial (Axipap)
- Author
-
Aude Flechon, C. Segura-Ferlay, Laurence Albiges, Bernard Escudier, Frederic Rolland, S. Dermeche, Alain Ravaud, Nathalie Rioux-Leclercq, M. Gross Goupil, D. Perol, Christine Chevreau, Ellen Blanc, G. Gravis, Sylvie Negrier, and Lionnel Geoffrois
- Subjects
0301 basic medicine ,medicine.medical_specialty ,business.industry ,Urology ,Hematology ,Axitinib ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,030220 oncology & carcinogenesis ,medicine ,business ,Renal carcinoma ,medicine.drug - Published
- 2018
80. Évolutions dans la prise en charge des métastases ganglionnaires cervicales sans cancer primitif retrouvé : doses et volumes cibles de la radiothérapie avec modulation d’intensité
- Author
-
C. Pflumio, P. Giraud, Emmanuel Babin, I. Troussier, Philippe Maingon, Jean-Christophe Faivre, E. Blais, L. Lahmi, Juliette Thariat, Lionnel Geoffrois, G. Klausner, and Sylvain Moriniere
- Subjects
medicine.medical_specialty ,Nodal irradiation ,business.industry ,medicine.medical_treatment ,Planning target volume ,Neck dissection ,Radiation therapy ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Unknown primary ,Medicine ,Radiology, Nuclear Medicine and imaging ,030212 general & internal medicine ,Intensity modulated radiotherapy ,Radiology ,business ,NODAL ,Lymph node - Abstract
The definition of nodal and/or mucosal target volumes for radiation therapy for lymphadenopathies of unknown primary is controversial. Target volumes may include all nodal areas bilaterraly and be pan-mucosal or unilateral, selective, including the sole oropharyngeal mucosa. This review presents current recommendations in light of changes in the TNM classification, Human papillomavirus status and therapeutic advances. We conducted a systematic review of the literature with the following keywords: lymphadenopathy; head and neck; unknown primary and radiation therapy. There are no direct comparative studies between unilateral or bilateral nodal irradiation or pan-mucosal and selective mucosal irradiation. Contralateral lymph node failure rates range from 0 to 6% after unilateral nodal irradiation and 0 and 31% after bilateral irradiation. Occurrence of a mucosal primary varies between 0 and 19.2%. Initial clinical presentation and Human papillomavirus status are critical to define mucosal target volumes. Intensity-modulated radiotherapy is recommended (rather than three-dimensional irradiation) to avoid toxicities. Systemic treatments have similar indications as for identified primary head and neck cancers. Failures do not appear superior in case of unilateral nodal irradiation but comparative studies are warranted due to major biases hampering direct comparisons. Human papillomavirus status should be incorporated into the therapeutic strategy and practice-changing TNM staging changes will need to be evaluated.
- Published
- 2018
81. Use of 18F-FDG PET/CT to select candidates for active surveillance: Results of the SEMITEP trial of PET-directed strategy for stage 1 seminoma
- Author
-
Yohann Loriot, Philippe Barthélémy, Karim Fizazi, Marine Gross Goupil, Emmanuelle Bompas, Sylvain Ladoire, Jérôme Rigaud, Stéphane Culine, Sophie Abadie Lacourtoisie, Aude Flechon, Gwenaelle Gravis, Emmanuelle Sevin, Christine Chevreau, Thierry Nguyen, Serena Grimaldi, Brigitte Laguerre, Hakim Mahammedi, Lionel Texier, Lionnel Geoffrois, and Carole Helissey
- Subjects
Cancer Research ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,macromolecular substances ,Seminoma ,medicine.disease ,carbohydrates (lipids) ,stomatognathic diseases ,Oncology ,Stage I Seminoma ,otorhinolaryngologic diseases ,medicine ,bacteria ,Fdg pet ct ,Radiology ,Stage (cooking) ,Relapse risk ,business ,Adjuvant - Abstract
4548Background: Stage I seminoma patients (pts) run a relapse risk of 15-20% without further adjuvant treatment. Pts are usually offered active surveillance or an adjuvant treatment with a risk of ...
- Published
- 2018
82. A phase II randomized trial of pembrolizumab versus cetuximab, concomitant with radiotherapy (RT) in locally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN): First results of the GORTEC 2015-01 'PembroRad' trial
- Author
-
Gabriel Waksi, Alexandre Coutte, X. Liem, Jean-François Ramée, Michel Rives, Franck Drouet, Xu Shan Sun, Jean Briac Prevost, Julian Biau, Elodie Vauleon, Yungan Tao, Jean Bourhis, Anne Auperin, Christian Sire, Jean-Marc Tourani, Laurent Martin, Cedrik Lafond, Marc Alfonsi, Lionnel Geoffrois, and Laura Sinigaglia
- Subjects
0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Cetuximab ,business.industry ,medicine.medical_treatment ,Locally advanced ,Pembrolizumab ,law.invention ,Radiation therapy ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Randomized controlled trial ,law ,030220 oncology & carcinogenesis ,Concomitant ,Internal medicine ,medicine ,Basal cell ,business ,Head and neck ,medicine.drug - Abstract
6018Background: Based on the hypothesis of a potential synergistic effect of the anti-PD1 pembrolizumab when combined with RT, this new combination was tested in a phase II randomized trial against...
- Published
- 2018
83. Safety and efficacy of nivolumab in metastatic renal cell carcinoma (mRCC): Results from the NIVOREN GETUG-AFU 26 study
- Author
-
Philippe Barthélémy, Bernard Escudier, Stéphane Oudard, Laurence Albiges, Sylvie Negrier, Delphine Borchiellini, Brigitte Laguerre, Marine Gross-Goupil, Christine Chevreau, Gwenaelle Gravis, Meryem Brihoum, Lionnel Geoffrois, and Cécile Dalban
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,030232 urology & nephrology ,medicine.disease ,Discovery and development of mTOR inhibitors ,Asymptomatic ,03 medical and health sciences ,Impaired renal function ,0302 clinical medicine ,Renal cell carcinoma ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,medicine.symptom ,Nivolumab ,business ,Prospective cohort study ,Clear cell - Abstract
577 Background: Nivolumab (N) has been approved for the treatment of mRCC after failure of 1 or 2 tyrosine kinase inhibitors (TKI) based on the results of Checkmate 025 study. Right after approval, we initiated the NIVOREN GETUG-AFU 26 study (NCT03013335), a French multicenter prospective study to evaluate safety and efficacy of N in a “real world setting”. Methods: Patients (pts) with clear cell mRCC could be enrolled if they had received at least one TKI. Compared with the pivotal trial, inclusion criteria allowed patients with more than 2 previous lines of treatment, including previous mTOR inhibitors, ECOG PS 2, asymptomatic brain metastases (BM) or impaired renal function. The primary objective of the study was the safety of N, efficacy being the main secondary objective. Between February 2016 and June 2017, 729 pts have been enrolled. We report the results from the first 528 pts. Results: All pts had clear cell mRCC, median age was 64, 77.2% were male. ECOG PS was > 1 in 73 pts (14.7%), 27.5% pts had received prior everolimus, 29.7% pts had received more than 2 previous lines, IMDC risk groups were 19%/54.9%/26.1% for good/intermediate and poor risk respectively; 69 (14%) pts had BM at screening. With a median follow up of 13.1 months, median duration of treatment was 4.1 months [0-15.6], with 31.4% of pts still on therapy. Treatment discontinuation due to adverse event (AE) occurred in (48) 13.3% pts . 64 serious related AE have been reported in 52 pts (9.9%) including 7 renal failures and 6 pneumonitis. Median PFS was 4.4 months 95%CI[3;4.6] . At the time of this analysis, 170 pts have died and 12 months OS rate was 66.4% 95%CI[ 61.7; 70.7]. In subgroups analysis, ECOG-PS > 1 (Hazard Ratio (HR) = 2.450 [1.704;3.523]), more than 2 previous lines (HR = 1.442 [1.059;1.963]) and prior use of everolimus (HR = 1.704 [1.250;2.322]) were associated with reduced OS in univariate analysis. Conclusions: We report the first analysis of the largest prospective real world setting study of N in mRCC. NIVOREN study demonstrates that N safety and efficacy in a “real world” prospective study are comparable to the pivotal study. Clinical trial information: NCT03013335.
- Published
- 2018
84. [Primary mediastinal germs cells tumors: a twenty years experience in a comprehensive cancer center]
- Author
-
Charlotte, Joly, Mathilde, Deblock, Emmanuel, Desandes, and Lionnel, Geoffrois
- Subjects
Adult ,Male ,Cancer Care Facilities ,Neoplasms, Germ Cell and Embryonal ,Vinblastine ,Mediastinal Neoplasms ,Drug Administration Schedule ,Seminoma ,Bleomycin ,Testicular Neoplasms ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Female ,Ifosfamide ,Cisplatin ,Neoplasm Recurrence, Local ,Retrospective Studies - Abstract
The aim of this study is to report treatments results of patients with primary germ cell tumors (GCTs) of mediastinum.A retrospective review was done of 19 consecutive patients with mediastinal GCTs treated in "Institut de cancérologie de Lorraine" between 1990 and 2012.A total of 19 patients were enrolled in this study. Three patients had pure seminoma and 16 patients had non-seminomatous germ cell tumors. All patients were treated with cisplatinum based chemotherapy at a dose of 33.48 mg/m(2)/week. At the end of chemotherapy, three patients (15.8%) had complete response and negative marker, seven of them (36.8%) had partial response and negative marker, five of them (26.32%) had partial response and positive marker, three of them (15.8%) had progressive disease (refractory disease) and one patient died because of the disease during treatment. The 1-year and 5-year overall survival rates were respectively 78 and 36% and the progression-free survival rate was 43%. When relapse occurred, this happened within a 13 month period.Our study confirmed the good management of mediastinal GCTs in our institute with similar results compared to literature.
- Published
- 2014
85. Personalised chemotherapy based on tumour marker decline in poor-prognosis germ-cell tumours: results of the GETUG 13 phase III trial
- Author
-
Maria Reckova, Guilhem Roubaud, Pierre Kerbrat, Claude Linassier, Jean-Christophe Eymard, Josef Mardiak, Christopher J. Logothetis, Anne Laure Martin, Karim Fizazi, Stéphane Culine, Christine Chevreau, Remy Delva, Florence Journeau, Jean Pierre Malhaire, Frederic Rolland, Gwenaelle Gravis, Agnès Laplanche, Christine Theodore, Lionnel Geoffrois, Aude Flechon, Lance C. Pagliaro, and Muriel Habibian
- Subjects
Male ,Organoplatinum Compounds ,medicine.medical_treatment ,Gastroenterology ,Chorionic Gonadotropin ,Granulocyte Colony-Stimulating Factor ,Antineoplastic Combined Chemotherapy Protocols ,Neoplasm Metastasis ,Precision Medicine ,Etoposide ,Peritoneal Neoplasms ,education.field_of_study ,Ifosfamide ,Middle Aged ,Neoplasms, Germ Cell and Embryonal ,Prognosis ,Recombinant Proteins ,Oxaliplatin ,Survival Rate ,Oncology ,Female ,alpha-Fetoproteins ,medicine.drug ,Adult ,medicine.medical_specialty ,Adolescent ,Paclitaxel ,Population ,Mediastinal Neoplasms ,Lenograstim ,Article ,Bleomycin ,Young Adult ,Testicular Neoplasms ,Internal medicine ,medicine ,Biomarkers, Tumor ,Humans ,education ,Survival rate ,Aged ,Neoplasm Staging ,Gynecology ,Chemotherapy ,business.industry ,International Agencies ,medicine.disease ,Regimen ,Cisplatin ,business ,Febrile neutropenia ,Follow-Up Studies - Abstract
Summary Background Poor prognosis germ-cell tumours are only cured in about half of patients. We aimed to assess whether treatment intensification based on an early tumour marker decline will improve progression-free survival for patients with germ-cell tumours. Methods In this phase 3, multicentre, randomised trial, patients were enrolled from France (20 centres), USA (one centre), and Slovakia (one centre). Patients were eligible if they were older than 16 years, had evidence of testicular, retroperitoneal, or mediastinal non-seminomatous germ cell tumours based on histological findings or clinical evidence and highly elevated serum human chorionic gonadotropin or alfa-fetoprotein concentrations that matched International Germ Cell Cancer Consensus Group poor prognosis criteria. After one cycle of BEP (intravenous cisplatin [20 mg/m 2 per day for 5 days], etoposide [100 mg/m 2 per day for 5 days], and intramuscular or intravenous bleomycin [30 mg per day on days 1, 8, and 15]), patients' human chorionic gonadotropin and alfa-fetoprotein concentrations were measured at day 18–21. Patients with a favourable decline in human chorionic gonadotropin and alfa-fetoprotein continued BEP (Fav-BEP group) for 3 additonal cycles, whereas patients with an unfavourable decline were randomly assigned (1:1) to receive either BEP (Unfav-BEP group) or a dose-dense regimen (Unfav-dose-dense group), consisting of intravenous paclitaxel (175 mg/m 2 over 3 h on day 1) before BEP plus intravenous oxaliplatin (130 mg/m 2 over 3 h on day 10; two cycles), followed by intravenous cisplatin (100 mg/m 2 over 2 h on day 1), intravenous ifosfamide (2 g/m 2 over 3 h on days 10, 12, and 14), plus mesna (500 mg/m 2 at 0, 3, 7 and 11 h), and bleomycin (25 units per day, by continuous infusion for 5 days on days 10–14; two cycles), with granulocyte-colony stimulating factor (lenograstim) support. Centrally blocked computer-generated randomisation stratified by centre was used. The primary endpoint was progression-free survival and the efficacy analysis was done in the intention-to-treat population. The planned trial accrual was completed in May, 2012, and follow-up is ongoing. This study is registered with ClinicalTrials.gov, number NCT00104676. Findings Between Nov 28, 2003, and May 16, 2012, 263 patients were enrolled and 254 were available for tumour marker assessment. Of these 51 (20%) had a favourable marker assessment, and 203 (80%) had an unfavourable tumour marker decline; 105 were randomly assigned to the Unfav-dose-dense group and 98 to the Unfav-BEP group. 3-year progression-free survival was 59% (95% CI 49–68) in the Unfav-dose-dense group versus 48% (38–59) in the Unfav-BEP group (HR 0·66, 95% CI 0·44–1·00, p=0·05). 3-year progression-free survival was 70% (95% CI 57–81) in the Fav-BEP group (HR 0·66, 95% CI 0·49–0·88, p=0·01 for progression-free survival compared with the Unfav-BEP group). More grade 3–4 neurotoxic events (seven [7%] vs one [1%]) and haematotoxic events occurred in the Unfav-dose-dense group compared with in the Unfav-BEP group; there was no difference in grade 1–2 febrile neutropenia (18 [17%] vs 18 [18%]) or toxic deaths (one [1%] in both groups). Salvage high-dose chemotherapy plus a stem-cell transplant was required in six (6%) patients in the Unfav-dose-dense group and 16 (16%) in the Unfav-BEP group. Interpretation Personalised treatment with chemotherapy intensification reduces the risk of progression or death in patients with poor prognosis germ-cell tumours and an unfavourable tumour marker decline. Funding Institut National du Cancer (Programme Hospitalier de Recherche Clinique).
- Published
- 2014
86. Postoperative brachytherapy alone and combined postoperative radiotherapy and brachytherapy boost for squamous cell carcinoma of the oral cavity, with positive or close margins
- Author
-
Lionnel Geoffrois, Elisabeth Luporsi, Severine Racadot, Marc A. Bollet, Bruno Toussaint, Sylvette Hoffstetter, Marie-Christine Kaminsky, Michel Lapeyre, Gilles Dolivet, and Didier Peiffert
- Subjects
Adult ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Brachytherapy ,Oral cavity ,Carcinoma ,medicine ,Humans ,Survival analysis ,Aged ,Retrospective Studies ,Aged, 80 and over ,Postoperative Care ,business.industry ,Radiotherapy Dosage ,Retrospective cohort study ,Neck dissection ,Middle Aged ,Prognosis ,medicine.disease ,Survival Analysis ,Surgery ,Radiation therapy ,Otorhinolaryngology ,Epidermoid carcinoma ,Carcinoma, Squamous Cell ,Neck Dissection ,Female ,Mouth Neoplasms ,Radiotherapy, Adjuvant ,Neoplasm Recurrence, Local ,Nuclear medicine ,business - Abstract
Postoperative radiotherapy is necessary for squamous cell carcinoma (SCC) of the oral cavity with positive or close margins. The aim of the study is to define the indications of postoperative brachytherapy (BRT).From 1979 to 1993, 82 patients with positive or close margins had postoperative BRT (58 T1-2, 24 T3-4, 45 mobile tongue, 37 floor of mouth). Forty-six patients had combined radiotherapy (RT) with a mean dose of 48 Gy, and BRT boost with a mean dose of 24 Gy. Thirty-six patients had BRT alone with a mean dose of 60 Gy. BRT was performed with interstitial low dose rate Iridium 192.Overall survival (OS), cause-specific survival (CSS), and local control (LC) at 5 years were, respectively, for T1-2/N0N- with BRT, 75%, 85%, and 88%,and with RT-BRT 70%, 92%, and 92%; for T1-2/N+ with RT-BRT, 44%, 67%, and 78%; for T3-4/N- with RT-BRT, 42%, 90%, and 80%; and for T3-4/N+ with RT-BRT, 22%, 43%, and 57%. Prognostic factors for OS, CSS, and LC were N+ (p/=.009), extracapsular spread (ECS+;p/=.000001), and T stage for LC only (p =.02). Prognostic factors for complications were a high number of wires with a cutoff at five wires (p =.008), a high dose rate with a cutoff at 0.57 Gy/hr (p =.01), and a high total dose (BRT + RT) with a cutoff at 71 Gy (p =.07).BRT alone for SCC T1-2/N0N- is better than RT-BRT because, with equivalent results, it avoids the adverse events of postoperative RT (xerostomia) and permits the treatment of a second head and neck primary in nonirradiated tissue. The results for the T3-4/N- are acceptable with this approach (ie, RT-BRT) but may be improved for N+.
- Published
- 2004
87. Concurrent Chemoradiation Therapy Versus Acceleration of Radiation Therapy With or Without Concurrent Chemotherapy in Locally Advanced Head and Neck Carcinoma (GORTEC 99-02): 7-Year Survival Data From a Phase 3 Randomized Trial and Prognostic Factors
- Author
-
Yungan Tao, M. Alfonsi, Christian Sire, G. Calais, Bernard Gery, O Dupuis, Michel Rives, Pierre Graff, Laurent Martin, C. Tuchais, P. Desprez, Stéphane Guerif, Lionnel Geoffrois, Etienne Bardet, Vincent Grégoire, Anne Auperin, Philippe Maingon, Jean Bourhis, and Michel Lapeyre
- Subjects
0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Radiation ,business.industry ,medicine.medical_treatment ,Locally advanced ,Concurrent chemoradiation ,law.invention ,Radiation therapy ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Concurrent chemotherapy ,Survival data ,Randomized controlled trial ,law ,030220 oncology & carcinogenesis ,Internal medicine ,Medicine ,Radiology, Nuclear Medicine and imaging ,business ,Head and neck carcinoma - Published
- 2016
88. Tumor Biomarker Association With Clinical Outcomes in Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC) Patients (Pts) Treated With Afatinib Versus Methotrexate (MTX): LUX-Head & Neck 1 (LHN1)
- Author
-
J.M. del Campo, Lionnel Geoffrois, Joël Guigay, X.J. Cong, Jérôme Fayette, Marco Merlano, Ezra E.W. Cohen, Flavio Solca, E. Ehrnrooth, Thomas Gauler, Makoto Tahara, Jaume Grau, Paul Clement, Lisa Licitra, Neil W. Gibson, Jan B. Vermorken, Barbara Burtness, Robert I. Haddad, Audrey Mailliez, and J-P. Machiels
- Subjects
0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Radiation ,business.industry ,Afatinib ,Medizin ,Head neck ,medicine.disease ,Head and neck squamous-cell carcinoma ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,Medicine ,Biomarker (medicine) ,Radiology, Nuclear Medicine and imaging ,Methotrexate ,business ,medicine.drug - Published
- 2016
89. Abstract 2719: Accelerated BRAF mutation analysis using a fully automated PCR platform improves the management of patients with metastatic melanoma : MELFAST trial
- Author
-
Julia Salleron, Lionnel Geoffrois, Agnès Leroux, Delphine Serre, Jean-Louis Merlin, Marie Husson, Alexandre Harlé, Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), and UNICANCER
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Metastatic melanoma ,business.industry ,medicine.drug_class ,[SDV]Life Sciences [q-bio] ,Operating procedures ,Cancer ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Dabrafenib ,Bioinformatics ,medicine.disease ,Tyrosine-kinase inhibitor ,3. Good health ,Fully automated ,Internal medicine ,medicine ,Personalized therapy ,10. No inequality ,Vemurafenib ,business ,neoplasms ,medicine.drug - Abstract
Background : Molecular diagnosis has become a standard of care in many cancers and BRAF mutations analysis in FFPE tumor specimens is needed to initiate personalized therapy using BRAF tyrosine kinase inhibitor (vemurafenib, dabrafenib) in BRAF-mutated metastatic melanoma. Accelerated BRAF mutation analysis is achievable using CE-IVD fully automated (FA) PCR-based platform (Idylla, Biocartis) and enables the determination of BRAF mutational status in less than 2 hours including sample preparation and proved suitable for routine molecular diagnosis of metastatic melanoma (Harlé et al. PloS ONE 11(4); e0153576). Patients and methods : MELFAST trial is an observational monocentric study aiming at evaluating the clinical impact of reducing BRAF status determination delay in patients with metastatic melanoma. 40 patients (pts) were included in MELFAST trial, 31 pts were included retrospectively with BRAF mutation analysis being performed according to standard operating procedures (SOP) using conventional PCR, 10 pts were included prospectively with BRAF mutation analysis being performed using FA-PCR. Results : Among the 40 pts included, 3 pts were excluded because of violation of inclusion criteria. 37 pts that were analyzed (29 pts with retrospective inclusion and 8 pts with prospective inclusion). BRAF mutational status was not known at the time of treatment decision in 11/29 (38%) pts included retrospectively and in all the pts included prospectively. Using FA-PCR enables to provide BRAF mutational status within the same day for most of the samples and the reporting delay was significantly reduced using FA-PCR as compared to SOP (0 vs 7 days, p Conclusion: As compared to conventional SOP, using FA-PCR accelerates BRAF mutation analysis reporting and significantly reduces the delay before initiation of personalized therapy in pts with metastatic melanoma. This warrants the investigation of the impact on the patients outcome i.e. progression free and overall survival. Citation Format: Alexandre Harlé, Delphine Serre, Julia Salleron, Marie Husson, Agnès Leroux, Lionnel Geoffrois, Jean-Louis Merlin. Accelerated BRAF mutation analysis using a fully automated PCR platform improves the management of patients with metastatic melanoma : MELFAST trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2719. doi:10.1158/1538-7445.AM2017-2719
- Published
- 2017
90. PREDICTOR (UNICANCER GEP11): Randomized phase II study of preoperative afatinib in untreated head and neck squamous cell carcinoma (HNSCC) patients
- Author
-
Nicolas Aide, Jean-Pierre Delord, Lionnel Geoffrois, Christophe Le Tourneau, Caroline Hoffmann, Olivier Malard, Ivan Bièche, Valerie Benavent, Jerzy Klijanienko, Olivier Capitain, Stéphane Temam, Laurent Laccourreye, Sébastien Vergez, Philippe Zrounba, Joël Guigay, Jocelyn Gal, Caroline Even, Frederic Rolland, Jérôme Fayette, and Gilles Dolivet
- Subjects
0301 basic medicine ,Antitumor activity ,Cancer Research ,medicine.drug_class ,business.industry ,Afatinib ,Phases of clinical research ,medicine.disease ,Head and neck squamous-cell carcinoma ,Tyrosine-kinase inhibitor ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,030220 oncology & carcinogenesis ,medicine ,Cancer research ,Methotrexate ,business ,medicine.drug - Abstract
6021 Background: Afatinib, a pan-HER irreversible tyrosine kinase inhibitor, demonstrated limited antitumor activity compared to methotrexate in unselected recurrent and/or metastatic HNSCC patients (LUX-HN1, Machiels et al, Lancet Oncol 2015). The UNICANCER (GEP 11) PREDICTOR study’s objective was to identify predictive and pharmacodynamic biomarkers of biological activity and efficacy of afatinib (EUDRACT N° 2010-024046-29). Methods: This open-label, randomized, multicentric, controlled, phase II study included untreated patients with operable T2-4N0-2M0 HNSCC of the oral cavity, pharynx and larynx, with a PS < 2, adequate organ function and LVEF > 50%. Patients were randomized (2:1) to: oral afatinib (A) 40mg/day (d) for 14-28d or no treatment (NT). Patients had pre-treatment tumor biopsies, tumor imaging, and PET CT scan, with a 2nd tumor imaging before surgery and a PET scan at D15. Adverse events were classified by NCI CTCAE criteria. Based on the biological primary endpoint of tumor reduction the sample size was designed to identify biomarkers associated with a 20% difference between the study arms. Results: 61 patients were included (A: 41/NT: 20). 2 patients in the NT arm were not analyzed (consent withdrawal, no surgery). 7 patients in arm A received < 14d of treatment, including 6 patients with unacceptable toxicity. Afatinib-related toxicities were: grade (G)1 37%, G2 41%, G3 7%, G4 5%, and G5 0%. G≥3 toxicities were mainly gastrointestinal. Partial responses (RECIST1.1) were observed in 3 patients (7.3%) in arm A versus none in the NT arm (p = 0.018). Progressive disease was not observed in arm A versus 3 (16.6%) in the NT arm. Partial responses on PET CT scan by PERCIST were observed in 15/31 evaluable patients (48%) in arm A versus 1/15 (6.7%) in the NT arm (p = 0.005). Conclusions: Afatinib given to HNSCC patients in the preoperative setting is safe and is associated with improved response according to RECIST1.1 and PERCIST compared to no treatment. Clinical trial information: NCT01415674.
- Published
- 2017
91. Efficacy and safety of nivolumab in patients with metastatic renal cell carcinoma (mRCC) and brain metastases: Preliminary results from the GETUG-AFU 26 (Nivoren) study
- Author
-
Gwenaelle Gravis, Muriel Habibian, Laurence Albiges, Delphine Borchiellini, Frederic Rolland, Sylvie Chabaud, Christine Chevreau, Bernard Escudier, Brigitte Laguerre, Marine Gross Goupil, Lionnel Geoffrois, Hakim Mahammedi, Sylvie Negrier, and Pierre Emmanuel Brachet
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Phases of clinical research ,macromolecular substances ,Brain ct ,03 medical and health sciences ,0302 clinical medicine ,Renal cell carcinoma ,Internal medicine ,otorhinolaryngologic diseases ,Medicine ,In patient ,Until Disease Progression ,business.industry ,medicine.disease ,Surgery ,carbohydrates (lipids) ,stomatognathic diseases ,030220 oncology & carcinogenesis ,Toxicity ,Nivolumab ,business ,Previously treated ,030217 neurology & neurosurgery - Abstract
4563 Background: Nivolumab (N) has been shown active in patients (pts) with mRCC after failure of 1 or 2 TKIs. Efficacy and safety of N in pts with brain metastases (BM) from RCC is still unknown. The aim of this study is to report preliminary data of the Nivoren study in pts with BM. Methods: GETUG-AFU 26 (Nivoren) is a prospective phase 2 study assessing safety and efficacy of N in a broader mRCC patient population than those recruited in the pivotal phase 3, including pts with BM (previously treated or not, but not requiring steroids), with previous mTOR inhibitor, with PS 2 as well as in previously highly pretreated pts. N was given every 2 weeks at 3mg/kg, until disease progression or unacceptable toxicity. Treatment was allowed beyond progression in case of clinical benefit. All pts had brain CT scan or MRI at baseline. Results: Up to December 2016 , 588 pts have been enrolled including 55 pts with BM (35 (67%) ,6 (12%) and 11 (21%) with 1, 2 or > 2 BM, respectively. Of those 55 pts, 10 pts (23%) were PS 2 and 25 (58%) PS 1, and 16 patients (29%) had received more that 2 lines of therapy. No previous treatment for BM was performed in 67% (n = 37), while 9% had previous brain surgery (n = 5 ;) or brain radiation (n = 17 (31%). 2/55 pts never received N. Median duration of therapy in BM pts was 2.4 months (varying from 0 to 9) with a 3-months PFS of 60% (IC95% = 45 – 73). Median OS is not reached at the time of this analysis. Among 44 pts with assessment of response on BM, 10 (23%) had objective response while 21 (48%) had local progressive disease. Neurologic deterioration requiring steroids was observed in 15 pts (32%) . Updated data will be presented at the meeting. Conclusions: This is the first large study to report preliminary safety and efficacy of N in RCC pts with BM. Safety of N in this pt population appears to be acceptable, although some pts do require steroids because of brain progressive disease. Objective response in the brain was observed in 23% of pts. Further follow up is required to determine the real benefit of N in this group of mRCC pts. Clinical trial information: NCT03013335.
- Published
- 2017
92. Impact of p16 expression on induction taxotere-cisplatin-5 FU (TPF) followed by cetuximab-radiotherapy in N2b-N3 head and neck squamous cell carcinoma (HNSCC): Results of GORTEC 2007-02 phase III randomized trial
- Author
-
Marie-Helene Girard-Calais, Yungan Tao, Laurent Martin, Cedrik Lafond, Christian Sire, Lionnel Geoffrois, Pascal Garaud, C. Tuchais, Jean Bourhis, Emmanuel Babin, Alexandre Coutte, Frederic Rolland, Odile Casiraghi, Dominique De Raucourt, Joelle Miny, and Philippe Maingon
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Locally advanced ,030218 nuclear medicine & medical imaging ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Cisplatin ,Cetuximab ,business.industry ,Induction chemotherapy ,medicine.disease ,Head and neck squamous-cell carcinoma ,Radiation therapy ,stomatognathic diseases ,Regimen ,030220 oncology & carcinogenesis ,business ,medicine.drug - Abstract
6070 Background: TPF is a reference induction chemotherapy regimen in non-operated locally advanced (LA) HNSCC. GORTEC 2007-02 phase III randomized trial was restricted to HNSCC patients with large nodal spread (N2b-N3). Results showed no benefit of 3 cycles of induction TPF followed by cetuximab-radiotherapy (RT), as compared to concurrent chemoradiotherapy (CRT) (Geoffrois et al ASCO 2016). Methods: Patients were randomized to receive concurrent CRT (arm A) or induction TPF followed by cetuximab-RT (arm B). RT was 70 Gy/35F/7 weeks. Concurrent chemotherapy was 3 cycles of carboplatin-5FU as previously described (Calais JNCI 1999). About 2/3 of patients had oropharyngeal cancers (OPC) and HPV status was determined in these patients using p16 expression as a surrogate (immunohistochemistry). Smoking status was also collected. Primary endpoint was progression free survival (PFS). Results: Between May 2009 and Aug 2013, 360 eligible patients were randomized including 231 (64%) OPC. Overall, p16 expression could be assessed in 172 / 231 OPC patients (74%) with 84 in arm A and 88 in arm B. 26 patients were found p16+ in arm A (31%) and 19 in arm B (22%). Only 8 out 45 (18%) p16+ patients were non-smokers showing that the large majority of OPC patients randomized were p16- (127/172) and smokers (117/129). A significant improvement in PFS was found in p16+ compared to p16- OPC (p < 0.0001). The absence of benefit in PFS associated with TPF + cetux-RT compared with CRT was suggested both in p16+ (HR: 0.78, 95% CI: 0.28 – 2.20) and in p16- OPC (HR: 1.28, 95% CI: 0.84 – 1.93), and the interaction between p16 and treatment modality was not significant (p = 0.35). A significant benefit was observed in favor of arm B regarding distant metastasis, but this effect was not different between the p16+ and p16- OPC, while there was no benefit of TPF + cetux-RT compared with CRT for loco-regional control, regardless of p16 status. Conclusions: The OPC p16 subpopulations were small. No benefit of induction TPF chemotherapy followed by cetuximab-RT compared with CRT in OPC patients regardless of p16 status. Clinical trial information: NCT01233843.
- Published
- 2017
93. PD-030: Survival of patients with head and neck cancers in France (EPICORL study)
- Author
-
Y. Pointreau, L. Lévy-Bachelot, M. Bec, Caroline Even, Florence Huguet, Michaël Schwarzinger, Stéphane Temam, Lionnel Geoffrois, and B. Le Vu
- Subjects
medicine.medical_specialty ,Oncology ,business.industry ,medicine ,Radiology, Nuclear Medicine and imaging ,Hematology ,Radiology ,Head and neck ,business - Published
- 2017
94. PO-136: Hospital costs associated with head and neck cancer by phase-of-care in France (EPICORL study)
- Author
-
L. Lévy-Bachelot, Florence Huguet, L. Sagaon Teyssier, Michaël Schwarzinger, Stéphane Temam, M. Bec, Caroline Even, Y. Pointreau, and Lionnel Geoffrois
- Subjects
medicine.medical_specialty ,Oncology ,business.industry ,Phase (matter) ,Head and neck cancer ,medicine ,Radiology, Nuclear Medicine and imaging ,Hematology ,medicine.disease ,business ,Surgery - Published
- 2017
95. Prise en charge des mucites après radiothérapie des cancers des voies aérodigestives supérieures
- Author
-
Lionnel Geoffrois, Michel Lapeyre, N. Pourel, M.C. Kaminsky, G. Dolivet, Christian Marchal, M. Simon, F. Maire, Pierre Bey, C. Charra-Brunaud, and B. Toussaint
- Subjects
Gynecology ,medicine.medical_specialty ,Upper aerodigestive tract ,Oncology ,business.industry ,Medicine ,Radiology, Nuclear Medicine and imaging ,Head and neck ,business ,Radiation injury - Abstract
Resume La mucite radio-induite lors de l’irradiation de la sphere ORL entraine chez les patients douleur, dysphagie, amaigrissement et asthenie. Ces dernieres annees, le traitement des cancers localement evolues non operables s'est intensifie (chimioradiotherapie, acceleration) et s'accompagne toujours d’une augmentation de la toxicite muqueuse. Plusieurs voies de recherche tentent de reduire les reactions muqueuses pourameliorer l’index therapeutique, mais aucune ne donne encore de resultats probants. Certains produits ou methodes testes semblent inefficaces (sucralfate, Chlorhexidine, CM-CSF sous-cutane, nitrate d’argent, prostaglandines, antioxydants, benzydamine hydrochloride), et d’autres paraissent prometteurs (povidone iodee, association d’antibiotiques locaux et antifongiques, glutamide, laser a basse energie, GM-CSF en bain de bouche, corticoides). Les radio-protecteurs donnent des resultats contradictoires et ne peuvent etre utilises en routine. Cependant, des recommandations peuvent etre proposees: la prise en charge globale initiale des patients doit etre systematique (hygiene alimentaire, remise en etat buccoclentaire, aide au sevrage, etc.). Des bains de bouche doivent etre realises d’emblee compte tenu de la modification de la flore buccale et pour eliminer la salive epaisse source de surinfection. Des produits antiseptiques non irritants doivent etre preferes (povidone iodee ou autre) et eventuellement des antibiotiques ou antifongiques (bicarbonates, amphotericine B ou autre). La mise en place d’une alimentation enterale preventive doit etre envisagee en cas de radiochimiotherapie concomitante ou d’acceleration. La douleur doit etre traitee. Enfin, la technique d’irradiation doit etre la plus adaptee a la situation (caches personnalises, radiotherapie conformationnelle et modulation d’intensite dans un proche avenir).
- Published
- 2001
96. Subcutaneous interleukin-2, interferon alfa-2a, and continuous infusion of fluorouracil in metastatic renal cell carcinoma: a multicenter phase II trial. Groupe Français d'Immunothérapie
- Author
-
Thierry Lesimple, Alain Ravaud, Claude Linassier, A. Caty, Jean-Marc Ferrero, Bruno Audhuy, Drevon M, Lionnel Geoffrois, J.-Y. Douillard, Sylvie Negrier, Christine Chevreau, Frédéric Gomez, and Bernard Escudier
- Subjects
Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Injections, Subcutaneous ,medicine.medical_treatment ,Alpha interferon ,Interferon alpha-2 ,Gastroenterology ,Renal cell carcinoma ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Infusions, Intravenous ,Carcinoma, Renal Cell ,Interferon alfa ,Aged ,Kidney ,Chemotherapy ,business.industry ,Interferon-alpha ,Middle Aged ,medicine.disease ,Kidney Neoplasms ,Recombinant Proteins ,Surgery ,Survival Rate ,Regimen ,medicine.anatomical_structure ,Oncology ,Fluorouracil ,Interleukin-2 ,Female ,business ,medicine.drug ,Kidney disease - Abstract
PURPOSE A phase II trial was designed to determine the efficacy and the tolerance of interleukin-2 (IL-2), interferon alfa-2a (IFNalpha), and fluorouracil (5-FU) in patients with metastatic renal cell carcinoma. PATIENTS AND METHODS One hundred eleven patients were included. Patients received subcutaneous IL-2 9 x 10(6) IU daily for 6 days and IFNalpha 6 x 10(6) IU on days 1, 3, and 5 every other week for 8 weeks. 5-FU was administered through a continuous infusion at 600 mg/m2 for 5 consecutive days for 1 week every 4 weeks. RESULTS The response rate was 1.8% (95% confidence interval [CI], 0% to 4.3%) with only two partial responses (PRs). Toxicity was moderate with 3.6% grade 4 events and two deaths related to treatment. CONCLUSION This regimen of IL-2, IFNalpha, and 5-FU in patients with metastatic renal cell carcinoma was ineffective. The results raise the question of the dose and schedule of subcutaneous cytokines that must be used in metastatic renal carcinoma.
- Published
- 1998
97. Mature results of the GETUG 13 phase III trial in poor-prognosis germ-cell tumors (GCT)
- Author
-
Frederic Rolland, Christopher J. Logothetis, Le Teuff, Lionnel Geoffrois, Aude Flechon, Jean-Christophe Eymard, Jozef Mardiak, Lance C. Pagliaro, Karim Fizazi, Gwenaelle Gravis, Stéphane Culine, Muriel Habibian, Gwenael, Christine Chevreau, Jean-pierre Malhaire, Guilhem Roubaud, Remy Delva, Claude Linassier, Pierre Kerbrat, Maria Reckova, and Christine Theodore
- Subjects
0301 basic medicine ,Oncology ,Cancer Research ,Poor prognosis ,medicine.medical_specialty ,business.industry ,Standard treatment ,medicine.disease ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Germ cell tumors ,business ,Tumor marker - Abstract
4504Background: Until 2014, standard treatment for poor-prognosis GCT was 4 BEP plus surgery and cure was achieved in only 50% of patients (pts) (IGCCCG 1997). The tumor marker decline rate identif...
- Published
- 2016
98. Induction docetaxel platinum 5-FU (TPF) followed by cetuximab-radiotherapy (cetux-RT) versus concurrent chemo-radiotherapy (CT/RT) in patients with N2b/c-N3 non operated stage III-IV squamous cell cancer of the head and neck (SCCHN): Results of the GORTEC 2007-02 phase III randomized trial
- Author
-
Frederic Rolland, Marie Helene Girard-Calais, Pascal Garaud, Joelle Miny, Philippe Maingon, Lionnel Geoffrois, Yungan Tao, Cedrik Lafond, Jean Bourhis, Dominique De Raucourt, Emmanuel Babin, C. Tuchais, Alexandre Coutte, Laurent Martin, and Christian Sire
- Subjects
0301 basic medicine ,Cancer Research ,medicine.medical_treatment ,law.invention ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Randomized controlled trial ,law ,medicine ,Stage (cooking) ,Cetuximab ,business.industry ,Cancer ,medicine.disease ,Carboplatin ,Radiation therapy ,stomatognathic diseases ,Regimen ,030104 developmental biology ,Oncology ,Docetaxel ,chemistry ,030220 oncology & carcinogenesis ,business ,Nuclear medicine ,medicine.drug - Abstract
6000Background: Both CT/RT, and cetux-RT have been established as standard treatments in non-operated locally advanced SCCHN. Taxotere-Platinum-5FU (TPF) is a reference induction regimen in this type of cancer and it is not known whether the addition of induction TPF followed by cetux-RT could improve the outcome of patients with locally advanced SCCHN, as compared to standard CT/RT. Methods: GORTEC 2007-02 trial was restricted to patients (pts) with palpable cervical nodes (N2b/c-N3) and was run in parallel with GORTEC 2007-01 randomized trial testing the addition of concurrent chemotherapy (CT) to cetux-RT in pts with N0-N2a disease. Selection criteria were pts fit for receiving CT with non-metastatic, non-operated stage III-IV SCC of oral cavity, oro/hypopharynx and larynx, regardless of HPV status. Pts were randomized to receive concurrent CT/RT (arm A) or induction TPF plus cetux-RT (arm B). RT was 70 Gy (2 Gy per day, 5 days per week). Concurrent CT was: 3 cycles of carboplatin 70mg/m²/d + 5FU 600mg...
- Published
- 2016
99. Contrasted outcomes to gefitinib on tumoral IGF1R expression in head and neck cancer patients receiving postoperative chemoradiation (GORTEC trial 2004-02)
- Author
-
René-Jean Bensadoun, Anne Sudaka, Anne Cayre, Marie-Christine Etienne-Grimaldi, Juliette Thariat, Lionnel Geoffrois, Dominique Grall, François Bertucci, Philippe Giraud, Sylvain Morinière, Ellen Van Obberghen-Schilling, Dominique de Raucourt, Olivier Dassonville, Gérard Milano, Séverine Racadot, Frédérique Penault-Llorca, Pascal Finetti, Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Service d'ORL, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Alexis Vautrin (CAV), Département de pharmacogénomique, Université Nice Sophia Antipolis (... - 2019) (UNS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU)
- Subjects
Oncology ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Randomization ,Antineoplastic Agents ,Placebo ,law.invention ,Receptor, IGF Type 1 ,03 medical and health sciences ,0302 clinical medicine ,Gefitinib ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Biomarkers, Tumor ,Humans ,Postoperative Period ,skin and connective tissue diseases ,Protein Kinase Inhibitors ,neoplasms ,[SDV.BDD]Life Sciences [q-bio]/Development Biology ,030304 developmental biology ,Aged ,Neoplasm Staging ,Cisplatin ,0303 health sciences ,business.industry ,Head and neck cancer ,Middle Aged ,medicine.disease ,Prognosis ,3. Good health ,respiratory tract diseases ,Clinical trial ,Treatment Outcome ,Head and Neck Neoplasms ,030220 oncology & carcinogenesis ,Quinazolines ,Biomarker (medicine) ,Female ,business ,medicine.drug ,Signal Transduction - Abstract
Purpose: Intermediate/high-risk operated patients with head and neck cancer may benefit from the addition of EGF receptor (EGFR) inhibitor gefitinib to chemoradiation. This study was designed to assess improved outcomes and identify predictive biomarkers. Experimental Design: Patients provided informed consent for tumor biomarker analyses and, when eligible, were further enrolled in the therapeutic CARISSA multicenter randomized phase II trial of postoperative irradiation with cisplatin + gefitinib (GORTEC 2004-02-NCT00169221). Results: Seventy-nine patients were included in the biomarker study, whereas 27 did not meet prerequisites for randomization between gefitinib and placebo. Two-year disease-free survival (DFS) rate was 65.0% and did not differ between randomized patients treated with gefitinib or placebo (P = 0.85). The similarity of DFS curves between nonrandomized patients (n = 27), randomized patients without gefitinib (n = 27), and randomized patients receiving gefitinib (n = 25), and similar histoclinical parameter distributions for all groups, allowed us to conduct statistical analyses on the entire population. On multivariate analysis, elevated expression of PAK1 by Western blotting, CD31 and membranous insulin-like growth factor 1 receptor (IGF1R) both by immunohistochemistry was significantly associated with shorter DFS. There was a significant interaction between IGF1R and gefitinib. Gefitinib abolished the prognostic discriminative power of high IGF1R expression; patients with elevated IGF1R expression benefited from gefitinib whereas those with low IGF1R fared worse. Conclusion: Gefitinib treatment affords no significant clinical benefit on DFS in an unselected population of patients with head and neck cancer. Our results point to the potential advantage of personalizing treatment for gefitinib based on tumoral IGF1R expression. This should foster confirmatory analyses in trials involving EGFR-targeting agents. Clin Cancer Res; 18(18); 5123–33. ©2012 AACR.
- Published
- 2012
100. Phase II study of figitumumab in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck: clinical activity and molecular response (GORTEC 2008-02)
- Author
-
Jean-Pascal Machiels, Joël Guigay, Marie-Christine Kaminsky-Forrett, Lionnel Geoffrois, Laurent Knoops, Emmanuelle Bompas, Sandra Schmitz, Sylvie Zanetta, Lionel Mignion, Marc Hamoir, Stéphanie Henry, and Anne Moxhon
- Subjects
Oncology ,medicine.medical_specialty ,Pathology ,Palliative care ,Biopsy ,Phases of clinical research ,Receptor, IGF Type 1 ,chemistry.chemical_compound ,Internal medicine ,medicine ,Carcinoma ,Humans ,Progression-free survival ,business.industry ,Reverse Transcriptase Polymerase Chain Reaction ,Gene Expression Profiling ,Head and neck cancer ,Cancer ,Antibodies, Monoclonal ,Immunoglobulins, Intravenous ,Hematology ,medicine.disease ,Head and neck squamous-cell carcinoma ,Figitumumab ,chemistry ,Head and Neck Neoplasms ,Carcinoma, Squamous Cell ,business - Abstract
BACKGROUND: Preclinical studies suggest that insulin-like growth factor-1 receptor (IGF-1R) blockage could be a promising therapeutic target in squamous cell carcinoma of the head and neck (SCCHN). Therefore, we investigated the efficacy and toxicity of figitumumab, an anti-IGF-1R monoclonal antibody, in palliative SCCHN. PATIENTS AND METHODS: Patients with palliative SCCHN progressing after platinum-based therapy were treated with figitumumab i.v. 20 mg/kg, every 3 weeks. The primary end point was the disease control rate at 6-8 weeks after treatment initiation. Tumor biopsies and plasma samples were collected before and after figitumumab administration to monitor the molecular response. RESULTS: Seventeen patients were included. Only two patients achieved stable disease at 6-8 weeks. Median overall survival and progression-free survival were 63 and 52 days, respectively. The main grade 3-4 adverse event was hyperglycemia (41%). Translational research showed that figitumumab downregulated IGF-1R at the surface of tumor cells with activation of the epidermal growth factor receptor (EGFR) pathway, as shown by the upregulation of p-EGFR in tumor cells (P = 0.016), and an increase in the plasma level of tumor growth factor-alpha (P = 0.006). CONCLUSION: Figitumumab monotherapy has no clinically significant activity in unselected palliative SCCHN.
- Published
- 2012
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.