139 results on '"Lionnel Geoffrois"'
Search Results
2. Personalized follow-up of circulating DNA in resected stage III/IV melanoma: PERCIMEL multicentric prospective study protocol
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Lionnel Geoffrois, Alexandre Harlé, Nassim Sahki, Aleksandra Sikanja, Florence Granel-Brocard, Alice Hervieu, Laurent Mortier, Géraldine Jeudy, Catherine Michel, Charlée Nardin, Cécile Huin-Schohn, and Jean-Louis Merlin
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Circulating tumor DNA ,Melanoma ,Adjuvant therapy ,Immunotherapy ,Kinase inhibitors ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background With more than 15,000 new cases /year in France and 2,000 deaths, cutaneous melanoma represents approximately 4% of incidental cancers and 1.2% of cancer related deaths. In locally advanced (stage III) or resectable metastatic (stage IV) melanomas, medical adjuvant treatment is proposed and recent advances had shown the benefit of anti-PD1/PDL1 and anti-CTLA4 immunotherapy as well as anti-BRAF and anti-MEK targeted therapy in BRAF V600 mutated tumors. However, the recurence rate at one year is approximately 30% and justify extensive research of predictive biomarkers. If in metastatic disease, the follow-up of circulating tumor DNA (ctDNA) has been demonstrated, its interest in adjuvant setting remains to be precised, especially because of a lower detection rate. Further, the definition of a molecular response could prove useful to personalized treatment. Methods PERCIMEL is an open prospective multicentric study executed through collaboration of the Institut de Cancérologie de Lorraine (non-profit comprehensive cancer center) and 6 French university and community hospitals. A total of 165 patients with resected stage III and IV melanoma, eligible to adjuvant imunotherapy or anti-BRAF/MEK kinase inhibitors will be included. The primary endpoint is the presence of ctDNA, 2 to 3 weeks after surgery, defined as mutated ctDNA copy number calculated as the allelic fraction of a clonal mutation relative to total ctDNA. Secondary endpoints are recurrence-free survival, distant metastasis-free survival and specific survival. We will follow ctDNA along treatment, quantitatively through ctDNA mutated copy number variation, qualitatively through the presence of cfDNA and its clonal evolution. Relative and absolute variations of ctDNA during follow-up will be also analyzed. PERCIMEL study aims at provide scientific evidence that ctDNA quantitative and qualitative variations can be used to predict the recurrence of patients with melanoma treated with adjuvant immunotherapy or kinase inhibitors, thus defining the notion of molecular recurrence.
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- 2023
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3. NISCAHN: a phase II trial of nivolumab in patients with salivary gland carcinoma (Unicancer ORL-08)
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Christian Borel, Caroline Even, Christophe Le Tourneau, Jerome Fayette, Laurence Bozec, Joël Guigay, Sylvie Chabaud, Laurence Digue, Lionnel Geoffrois, Fréderic Rolland, Didier Cupissol, Anne Françoise Dillies, Sylvie Zanetta, Sophie Couchon-Thaunat, Valérie Costes-Martineau, Anne Sudaka-Bahadoran, Isabelle Jallut, Florence Garic, and Audrey Lardy-Cleaud
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Objective Salivary gland cancers (SGC) are rare cancers with currently no standard treatment for recurrent/metastatic disease. Based on checkpoint inhibitors benefit in a broad range of tumours, NIvolumab in Salivary gland CArcinoma of the Head and Neck (NISCAHN) evaluated nivolumab efficacy in SGC.Methods and analysis In this phase II single-stage Fleming design, patients with SGC with a progressive disease progression within 6 months prior to entering the study, were divided into ACC (adenoid cytic carcinoma) and non-ACC. All received nivolumab for a maximum of 12 months. The primary endpoint was the non-progression rate at 6 months (NPR6m) according to Response Evaluation Criteria in Solid Tumors V.1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS), overall response rate (ORR), tumour growth rate, safety and quality of life (health-related quality of life).Results 46 patients with ACC and 52 patients without ACC were enrolled over 1 year. Median follow-up was respectively 29.2 months and 16.9 months for patients with ACC and non-ACC. In the ACC cohort, with 15/45 patients non-progressive at 6 months, the primary endpoint was met (33.3%; 95% CI 21.8 to NE). Nivolumab failed to demonstrate efficacy in the non-ACC cohort (NPR6m: 14.0%; 7/50 patients). ORR, PFS and OS were 8.7% (95% CI 2.4 to 20.8), 5.3 (95% CI 3.2 to 5.6) and 17.2 months (95% CI 12.5-NE) in the ACC cohort, and 3.8% (95% CI 0.5 to 13.2), 1.8 (95% CI 1.7 to 3.5) and 11.5 months (95% CI 7.5 to 14.8) in the non-ACC cohort. Nivolumab safety profile was consistent with previous reports.Conclusion Nivolumab has limited efficacy in SGC. Differential results were observed in the two cohorts. The primary endpoint was met in the ACC cohort and no new safety signals were identified.Trial registration number EudraCT number: 2016-001794-32/NCT03132038.
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- 2023
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4. Comprehensive analyses of immune tumor microenvironment in papillary renal cell carcinoma
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Laurence Albiges, Bernard Escudier, Gwenaelle Gravis, Ronan Flippot, Alain Ravaud, Maxime Meylan, Nathalie Rioux-Leclercq, Marine Gross-Goupil, Gaëlle Fromont, Christophe Passot, Lionnel Geoffrois, Fréderic Rolland, Manon de Vries-Brilland, Jonathan Dauvé, Elena Spirina-Menand, Christine Chevreau, Ellen Blanc, Félix Lefort, and Sylvie Negrier
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background Papillary renal cell carcinoma (pRCC) is the most common non-clear cell RCC, and associated with poor outcomes in the metastatic setting. In this study, we aimed to comprehensively evaluate the immune tumor microenvironment (TME), largely unknown, of patients with metastatic pRCC and identify potential therapeutic targets.Methods We performed quantitative gene expression analysis of TME using Microenvironment Cell Populations-counter (MCP-counter) methodology, on two independent cohorts of localized pRCC (n=271 and n=98). We then characterized the TME, using immunohistochemistry (n=38) and RNA-sequencing (RNA-seq) (n=30) on metastatic pRCC from the prospective AXIPAP trial cohort.Results Unsupervised clustering identified two “TME subtypes”, in each of the cohorts: the “immune-enriched” and the “immune-low”. Within AXIPAP trial cohort, the “immune-enriched” cluster was significantly associated with a worse prognosis according to the median overall survival to 8 months (95% CI, 6 to 29) versus 37 months (95% CI, 20 to NA, p=0.001). The two immune signatures, Teff and JAVELIN Renal 101 Immuno signature, predictive of response to immune checkpoint inhibitors (CPI) in clear cell RCC, were significantly higher in the “immune-enriched” group (adjusted p
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- 2023
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5. Factors associated with under-reporting of head and neck squamous cell carcinoma in cause-of-death records: A comparative study of two national databases in France from 2008 to 2012.
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Caroline Even, Luis Sagaon Teyssier, Yoann Pointreau, Stéphane Temam, Florence Huguet, Lionnel Geoffrois, Michaël Schwarzinger, and EPICORL Study Group
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Medicine ,Science - Abstract
ObjectiveTo date, no study has evaluated the detection rate of head and neck squamous cell carcinoma (HNSCC) in cause-of-death records in Europe. Our objectives were to compare the number of deaths attributable to HNSCC from two national databases in France and to identify factors associated with under-reporting of HNSCC in cause-of-death records.MethodsThe national hospital discharge database and the national underlying cause-of-death records were compared for all HNSCC-attributable deaths in adult patients from 2008 to 2012 in France. Factors associated with under-reporting of HNSCC in cause-of-death records were assessed using multivariate Poisson regression.ResultsA total of 41,503 in-hospital deaths were attributable to HNSCC as compared to 25,647 deaths reported in national UCoD records (a detection rate of 62%). Demographics at death were similar in both databases with respect to gender (83% men), age (54% premature deaths at 25-64 years), and geographic distribution. In multivariate Poisson regression, under-reporting of HNSCC in cause-of-death records significantly increased in 2012 compared to 2010 (+7%) and was independently associated with a primary HNSCC site other than the larynx, a former primary or second synchronous cancer other than HNSCC, distant metastasis, palliative care, and death in hospitals other than comprehensive cancer care centers. The main study results were robust in a sensitivity analysis which also took into account deaths outside hospital (overall, 51,129 HNSCC-attributable deaths; a detection rate of 50%). For the year 2012, the age-standardized mortality rate for HNSCC derived from underlying cause-of-death records was less than half that derived from hospital discharge summaries (14.7 compared to 34.1 per 100,000 for men and 2.7 compared to 6.2 per 100,000 for women).ConclusionHNSCC is largely under-reported in cause-of-death records. This study documents the value of national hospital discharge databases as a complement to death certificates for ascertaining cancer deaths.
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- 2021
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6. Efficacy and safety of nivolumab in bone metastases from renal cell carcinoma: Results of the GETUG-AFU26-NIVOREN multicentre phase II study
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Maud Velev, Cécile Dalban, Christine Chevreau, Gwenaelle Gravis, Sylvie Negrier, Brigitte Laguerre, Marine Gross-Goupil, Sylvain Ladoire, Delphine Borchiellini, Lionnel Geoffrois, Florence Joly, Frank Priou, Philippe Barthelemy, Mathieu Laramas, Berangère Narciso, Antoine Thiery-Vuillemin, Jean-François Berdah, Victoria Ferrari, Quentin Dominique Thomas, Cécile Mione, Hubert Curcio, Stephane Oudard, Florence Tantot, Bernard Escudier, Sylvie Chabaud, Laurence Albiges, and Constance Thibault
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Cancer Research ,Oncology - Published
- 2023
7. Efficacy and Safety of Concomitant Proton Pump Inhibitor and Nivolumab in Renal Cell Carcinoma: Results of the GETUG-AFU 26 NIVOREN Multicenter Phase II Study
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Elie Rassy, Cécile Dalban, Emeline Colomba, Lisa Derosa, Carolina Alves Costa Silva, Sylvie Negrier, Christine Chevreau, Gwenaelle Gravis, Stephane Oudard, Brigitte Laguerre, Philippe Barthelemy, Marine Gross Goupil, Lionnel Geoffrois, Frederic Rolland, Antoine Thiery-Vuillemin, Florence Joly, Sylvain Ladoire, Florence Tantot, Bernard Escudier, and Laurence Albiges
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Male ,Nivolumab ,Oncology ,Urology ,Humans ,Female ,Proton Pump Inhibitors ,Carcinoma, Renal Cell ,Immune Checkpoint Inhibitors ,Kidney Neoplasms ,Retrospective Studies - Abstract
Proton pump inhibitors (PPI) may influence the gut microbiome and thus impact the effectiveness of immune checkpoint inhibitors (ICI). The effect of PPIs on the outcomes of ICI has not been fully explored and investigated in metastatic renal cell carcinoma (mRCC).This retrospective analysis used prospectively collected data from the GETUG-AFU 26 NIVOREN (NCT03013335) phase II study which enrolled 729 mRCC patients of whom 720 were treated with nivolumab. The main objective of this analysis was to evaluate the impact of PPI on the efficacy and safety outcomes of mRCC patients. PPI use was defined as PPI administration on the day of ICI initiation.Of the 707 patients with mRCC analyzed in this study, 196 (27.7%) were PPI users. The majority of PPI users were males (80.6%), had an ECOG performance status of 0-1 (78.9%) and a nephrectomy (82.1%). Almost two-thirds of the patients had a favorable and intermediate IMDC risk category and 52% received nivolumab in the third line and beyond. PPI use did not correlate with PFS or OS (HR = 0.89, 95% CI 0.74-1.08 and HR = 1.24; 95% CI, 0.98-1.58, respectively). Grade 3-5 nivolumab-related adverse events were more common among PPI users (25.5% vs. 15.3%).This real-world study suggests that PPI use in patients with mRCC does not impact the efficacy outcomes but may influence the safety of nivolumab which warrants further investigations.
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- 2022
8. Oncological Outcomes of Delayed Nephrectomy After Optimal Response to Immune Checkpoint Inhibitors for Metastatic Renal Cell Carcinoma
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Géraldine, Pignot, Antoine, Thiery-Vuillemin, Laurence, Albigès, Jochen, Walz, Hervé, Lang, Loïc, Balssa, Bastien, Parier, Lionnel, Geoffrois, Karim, Bensalah, Friederike, Schlürmann, Sylvain, Ladoire, Pierre, Bigot, Delphine, Borchiellini, Ophélie, Cassuto, Constance, Thibault, Alexandre, Ingels, Véronique, Saldana, Guilhem, Roubaud, Jean-Christophe, Bernhard, Gwenaelle, Gravis, and Philippe, Barthélémy
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Nivolumab ,Oncology ,Urology ,Humans ,Radiology, Nuclear Medicine and imaging ,Surgery ,Carcinoma, Renal Cell ,Immune Checkpoint Inhibitors ,Ipilimumab ,Nephrectomy ,Protein Kinase Inhibitors ,Kidney Neoplasms ,Retrospective Studies - Abstract
In the current era of immune checkpoint inhibitors (ICIs), the role and optimal timing of a nephrectomy in patients with metastatic renal cell carcinoma (mRCC) remain unknown.To assess the oncological outcomes of patients who responded to ICI-based treatments and were subsequently treated with a delayed nephrectomy.This national retrospective evaluation included 30 patients with mRCC who underwent a nephrectomy after a complete response (CR) or a major partial response (80%) to ICI treatment at metastatic sites.Partial or radical nephrectomy after a favorable response to ICI treatment.Disease-free survival (DFS), progression-free survival (PFS), overall survival (OS), and potential discontinuation of systemic treatment were assessed.ICI-based treatments included ipilimumab-nivolumab (40%), ICI + tyrosine kinase inhibitor (10%), and nivolumab (50%). A delayed nephrectomy was performed after a median ICI treatment duration of 10 mo. In 19 cases (63.3%), surgeons faced difficulties due to adhesions or inflammatory changes. A complete pathological response was observed in 16.7% of patients. After a median follow-up of 19.5 mo after nephrectomy, 76.7% of patients achieved DFS. At 1 yr, 66.7% of patients were free from systemic treatment. The PFS and OS rates were, respectively, 96.7% and 100% at 1 yr, and 78.3% and 86.1% at 2 yr. Patients with a CR at metastatic sites had a better prognosis than those with a major partial response, in terms of DFS (p = 0.022) and PFS (p = 0.014).Despite potentially challenging surgery, a delayed nephrectomy for patients who responded to ICI treatment provided promising oncological outcomes, and the majority of patients could discontinue systemic treatment.In this study, we evaluated the clinical outcome in patients who responded well to immunotherapy, and subsequently underwent kidney ablation surgery. Three-quarters of patients experienced no recurrence, and in most cases, medical treatment could be discontinued.
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- 2022
9. Supplementary Table 1 from Contrasted Outcomes to Gefitinib on Tumoral IGF1R Expression in Head and Neck Cancer Patients Receiving Postoperative Chemoradiation (GORTEC Trial 2004-02)
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Gérard Milano, Ellen Van Obberghen-Schilling, Anne Sudaka, Sylvain Morinière, Séverine Racadot, Philippe Giraud, Pascal Finetti, Lionnel Geoffrois, Dominique De Raucourt, Anne Cayre, Francois Bertucci, Olivier Dassonville, Frédérique Penault-Llorca, Dominique Grall, Marie-Christine Etienne-Grimaldi, René-Jean Bensadoun, and Juliette Thariat
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PDF file, 31K, Description of mean median min and max values for each biomarker.
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- 2023
10. Data from Contrasted Outcomes to Gefitinib on Tumoral IGF1R Expression in Head and Neck Cancer Patients Receiving Postoperative Chemoradiation (GORTEC Trial 2004-02)
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Gérard Milano, Ellen Van Obberghen-Schilling, Anne Sudaka, Sylvain Morinière, Séverine Racadot, Philippe Giraud, Pascal Finetti, Lionnel Geoffrois, Dominique De Raucourt, Anne Cayre, Francois Bertucci, Olivier Dassonville, Frédérique Penault-Llorca, Dominique Grall, Marie-Christine Etienne-Grimaldi, René-Jean Bensadoun, and Juliette Thariat
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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.
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- 2023
11. Impact of the app-based and nurse-led supportive care program AKO@dom on dose intensity of oral-targeted therapies in patients with metastatic renal cell cancer: a multicentric observational retrospective study
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Victor Gaillard, Albane Lhuillier, Cécile Bigot, Laure Pierard, Philippe Trensz, Mickael Burgy, Caroline Schuster, Gabriel Malouf, Aurélie Fritsch, Hervé Lang, Thibault Tricard, Delphine Borchiellini, Lionnel Geoffrois, and Philippe Barthelemy
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Axitinib ,Oncology ,Sunitinib ,Humans ,Antineoplastic Agents ,Carcinoma, Renal Cell ,Mobile Applications ,Nurse's Role ,Protein Kinase Inhibitors ,Kidney Neoplasms ,Aged ,Retrospective Studies - Abstract
Tyrosine kinase inhibitors (TKIs) remain a cornerstone of metastatic kidney cancer (mRCC). Adverse events (AEs) may lead to dose downregulation, and optimal management of AEs is needed to maintain an efficient dose intensity (DI). The aim of our study was to evaluate the impact of an app-based and nurse-led supportive-care program on DI in mRCC patients.This multicenter (n = 3), retrospective study evaluated all consecutive mRCC patients who participated in the AKO@dom program, which consisted of an app-based and nurse-led weekly patient evaluation at home during the first 3 months of TKI intake. Treatment patterns and modifications were described, and the mean DI (mDI) was calculated at the end of AKO@dom.Eighty-nine patients were included: 12 had sunitinib, 18 pazopanib, 12 axitinib, and 47 cabozantinib. Median age was 69 years (60-76). TKIs were mainly initiated at standard doses except for cabozantinib (53% started at 40 mg/day); 71% had prior systemic treatment. Nine patients discontinued permanent treatment during the program. Thirty-two patients required ≥ 1 dose interruption, and 29% experienced ≥ 1 grade 3 AE of any type. The mDI (in mg/day) at 3 months was 34.4 ± 17.7 for sunitinib, 672.8 ± 144 for pazopanib, 8.6 ± 2.6 for axitinib, and 40 (36-48) for cabozantinib. Fifty-five patients [68.75% (95% CI: 57-78%)] had a mDI ≥ than reported in the literature. Overall survival at 12 months was 64.2% (CI 95%: 55-75%).The AKO@dom program allowed 68.75% of patients to maintain a high dose intensity after 3 months of TKI treatment. The impact on survival outcomes needs to be evaluated in randomized clinical trials.
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- 2022
12. Extended follow-up of a phase 2 trial of xevinapant plus chemoradiotherapy in high-risk locally advanced squamous cell carcinoma of the head and neck: a randomised clinical trial
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Yungan TAO, Xu-Shan Sun, Yoann Pointreau, Christophe Le Tourneau, Christian Sire, Marie-Christine Kaminsky, Alexandre Coutte, Marc Alfonsi, Benôit Calderon, Pierre Boisselier, Laurent Martin, Jessica Miroir, Jean-Francois Ramee, Jean-Pierre Delord, Florian Clatot, Frederic Rolland, Julie Villa, Nicolas Magne, Olgun Elicin, Elisabeta Gherga, France Nguyen, Cédrik Lafond, Guillaume Bera, Valentin Calugaru, Lionnel Geoffrois, Bruno Chauffert, Lars Damstrup, Philippa Crompton, Abdallah Ennaji, Kathrin Gollmer, Heidi Nauwelaerts, Jean Bourhis, Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Jean Bernard [Institut Inter-régional de Cancérologie - Le Mans], Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, CHU Amiens-Picardie, CHirurgie, IMagerie et REgénération tissulaire de l’extrémité céphalique - Caractérisation morphologique et fonctionnelle - UR UPJV 7516 (CHIMERE), Université de Picardie Jules Verne (UPJV), Institut Sainte Catherine [Avignon], Institut du Cancer de Montpellier (ICM), Aix-Marseille Université - Faculté de pharmacie (AMU PHARM), Aix Marseille Université (AMU), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Département d'oncologie médicale [Rouen], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), and Centre Hospitalier Universitaire [Grenoble] (CHU)
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Xevinapant ,Cancer Research ,Efficacy ,Survival ,Oncology ,Locally advanced squamous cell carcinoma of the head and neck ,610 Medicine & health ,Chemoradiotherapy ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
International audience; Introduction: We report long-term efficacy and overall survival (OS) results from a randomised, double-blind, phase 2 study (NCT02022098) investigating xevinapant plus standard-of-care chemoradiotherapy (CRT) vs. placebo plus CRT in 96 patients with unresected locally advanced squamous cell carcinoma of the head and neck (LA SCCHN).Methods: Patients were randomised 1:1 to xevinapant 200 mg/day (days 1-14 of a 21-day cycle for 3 cycles), or matched placebo, plus CRT (cisplatin 100 mg/m2 every 3 weeks for 3 cycles plus conventional fractionated high-dose intensity-modulated radiotherapy [70 Gy/35 F, 2 Gy/F, 5 days/week for 7 weeks]). Locoregional control, progression-free survival, and duration of response after 3 years, long-term safety, and 5-year OS were assessed.Results: The risk of locoregional failure was reduced by 54% for xevinapant plus CRT vs. placebo plus CRT but did not reach statistical significance (adjusted hazard ratio [HR] 0.46; 95% CI, 0.19-1.13; P = .0893). The risk of death or disease progression was reduced by 67% for xevinapant plus CRT (adjusted HR 0.33; 95% CI, 0.17-0.67; P = .0019). The risk of death was approximately halved in the xevinapant arm compared with placebo (adjusted HR 0.47; 95% CI, 0.27-0.84; P = .0101). OS was prolonged with xevinapant plus CRT vs. placebo plus CRT; median OS not reached (95% CI, 40.3-not evaluable) vs. 36.1 months (95% CI, 21.8-46.7). Incidence of late-onset grade ≥3 toxicities was similar across arms.Conclusions: In this randomised phase 2 study of 96 patients, xevinapant plus CRT demonstrated superior efficacy benefits, including markedly improved 5-year survival in patients with unresected LA SCCHN.
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- 2023
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13. Chemotherapy for Muscle-invasive Bladder Cancer: Impact of Cisplatin Delivery on Renal Function and Local Control Rate in the Randomized Phase III VESPER (GETUG-AFU V05) Trial
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Sophie Abadie-Lacourtoisie, Thierry Nguyen-Tan-Hon, Jean-Philippe Spano, Olivier Huillard, Nadine Houede, Hakim Mahammedi, Eric Voog, Yohann Loriot, Tifenn Lharidon, Sheik Emambux, Stéphane Culine, Lionnel Geoffrois, Jean-Christophe Eymard, Mounira El Demery, V. Harter, Vesper Trial Investigators, Philippe Barthélémy, Brigitte Laguerre, Yves Allory, Christine Chevreau, Aline Guillot, Florence Joly, Frédéric Di Fiore, Carolina Saldana, Gwenaelle Gravis, Christian Pfister, Werner Hilgers, Camille Serrate, Guilhem Roubaud, Sabine Vieillot, Aude Fléchon, Frederic Rolland, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Département cancer environnement (Centre Léon Bérard - Lyon), Centre Léon Bérard [Lyon], Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Département d'oncologie médicale [Rennes], CRLCC Eugène Marquis (CRLCC), Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Hôpital Charles Nicolle [Rouen], Institut Bergonié [Bordeaux], CHU Strasbourg, Clinique Victor Hugo [Le Mans], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Groupe Hospitalier Diaconesses Croix Saint-Simon, CHU Henri Mondor, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse (U981), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Jean Godinot [Reims], Sorbonne Université (SU), Hôpital Cochin [AP-HP], 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), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service d'Oncologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Institut Sainte Catherine [Avignon], Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre d'Investigation Clinique [CHU Rouen] (CIC Rouen), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)
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MESH: Muscles ,medicine.medical_treatment ,Pathological downstaging ,Kidney ,[SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology ,Antineoplastic Combined Chemotherapy Protocols ,Medicine ,Muscles ,Combination chemotherapy ,Neoadjuvant Therapy ,Cisplatin-based chemotherapy ,MESH: Urinary Bladder Neoplasms ,Vinblastine ,MESH: Antineoplastic Combined Chemotherapy Protocols ,MESH: Methotrexate ,Oncology ,MESH: Chemotherapy, Adjuvant ,Chemotherapy, Adjuvant ,medicine.drug ,Neoadjuvant treatment ,medicine.medical_specialty ,Urology ,MESH: Neoadjuvant Therapy ,MESH: Vinblastine ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Cystectomy ,MESH: Doxorubicin ,Humans ,Retrospective Studies ,Cisplatin ,Chemotherapy ,Pathological complete response ,Perioperative chemotherapy ,MESH: Humans ,Bladder cancer ,business.industry ,MESH: Cystectomy ,MESH: Retrospective Studies ,MESH: Kidney ,medicine.disease ,Gemcitabine ,Methotrexate ,MESH: Cisplatin ,Urinary Bladder Neoplasms ,Doxorubicin ,business - Abstract
Background : Cisplatin-based combination chemotherapy before surgery is the standard of care for muscle-invasive bladder cancer. However, the optimal chemotherapy modalities have not been precisely defined to date. Patients and Methods : In the VESPER trial, patients received after randomization either gemcitabine and cisplatin (GC, 4 cycles) or methotrexate, vinblastine, doxorubicin and cisplatin (dose dense [dd]-MVAC, 6 cycles). Creatinine clearance (CrCl) was calculated before each cycle according to the Cockroft and Gault formula. Definition criteria for local control after neoadjuvant chemotherapy included pathological complete response (ypT0N0), pathological downstaging ( Results : A total of 2,128 cycles of chemotherapy were delivered, including 2,120 (99.6%) with cisplatin. Full doses of cisplatin were given in 1866 (88%) cycles. Twenty-three (4.7%) patients had to stop chemotherapy (12 GC, 11 dd-MVAC) because of renal failure. No difference in CrCl median values was observed between the two regimens during the first four cycles. A mild decrease occurred thereafter in patients treated with two additional cycles of dd-MVAC. A minimum total dose of 270 mg/m2 for cisplatin was mandatory to optimize pathological complete responses. Conclusion : At least 4 cycles of cisplatin-based chemotherapy should be delivered before cystectomy. Increasing the number of cycles beyond 4 cycles does not lead to a clinically significant deterioration in renal function but without obvious gain on local control. MicroAbstractCGC : A deep analysis of data from a randomized trial of perioperative chemotherapy in muscle-invasive bladder cancer shows that a minimum number of 4 cycles is required to optimize the chances of pathological complete response at cystectomy. Increasing the number beyond 4 cycles does not lead to a clinically significant deterioration in renal function without any obvious gain on pathological complete response.
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- 2021
14. Sunitinib Alone or After Nephrectomy for Patients with Metastatic Renal Cell Carcinoma: Is There Still a Role for Cytoreductive Nephrectomy?
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Bernard Escudier, Laurent Guy, Arnaud Mejean, Thierry Lebret, Brigitte Laguerre, Laurence Albiges, Jean-Marc Tréluyer, Marine Gross-Goupil, Eric Lechevallier, Claude Linassier, Alain Ravaud, Karim Bensalah, Antoine Thiery-Vuillemin, Marc-Olivier Timsit, Stéphane Oudard, Lionnel Geoffrois, Frederic Rolland, Sandra Colas, Christine Chevreau, Simon Thezenas, Luc Cormier, Jean-Christophe Bernhard, Hervé Lang, Gwenaelle Gravis, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), CHU Gabriel Montpied [Clermont-Ferrand], and CHU Clermont-Ferrand
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medicine.medical_specialty ,[SDV]Life Sciences [q-bio] ,Urology ,medicine.medical_treatment ,Population ,030232 urology & nephrology ,Antineoplastic Agents ,urologic and male genital diseases ,Nephrectomy ,03 medical and health sciences ,0302 clinical medicine ,Renal cell carcinoma ,Sunitinib ,medicine ,Clinical endpoint ,Humans ,Risk factor ,education ,Carcinoma, Renal Cell ,ComputingMilieux_MISCELLANEOUS ,Retrospective Studies ,education.field_of_study ,business.industry ,Hazard ratio ,Cytoreduction Surgical Procedures ,medicine.disease ,Kidney Neoplasms ,female genital diseases and pregnancy complications ,3. Good health ,Clinical trial ,030220 oncology & carcinogenesis ,business ,medicine.drug - Abstract
Background The CARMENA trial in patients with metastatic renal cell carcinoma (mRCC) demonstrated that treatment with sunitinib alone was noninferior to cytoreductive nephrectomy (CN) followed by sunitinib (nephrectomy⬜sunitinib). Objective The objective of this study was to provide updated overall survival (OS) outcomes of CARMENA and assess whether some subgroups may still benefit from upfront CN. Design, setting, and participants CARMENA was a phase III trial in 450 patients with mRCC enrolled from 2009 to 2017. Intervention Patients in the intention-to-treat population received nephrectomy⬜sunitinib (standard of care [SOC]; n = 226) or sunitinib alone (n = 224). Outcome measurements and statistical analysis Primary endpoint was OS, assessed using an updated data cut-off (October 2018; median OS event-free follow-up, 36.6 mo). Patients were reclassified by risk using International Metastatic RCC Database Consortium (IMDC) criteria. Results and limitations Sunitinib alone was noninferior to nephrectomy⬜sunitinib (hazard ratio [HR], 0.97; 95% confidence interval, 0.79⬜1.19; p = 0.8) and demonstrated longer median OS (19.8 mo vs 15.6 mo, respectively). For patients with two or more IMDC risk factors, OS was significantly longer with sunitinib alone than with nephrectomy⬜sunitinib (31.2 mo vs 17.6 mo, respectively; HR, 0.65; p = 0.03). For patients with one IMDC risk factor, OS was longer for nephrectomy⬜sunitinib versus sunitinib alone although not significantly (31.4 mo vs 25.2 mo; HR, 1.30; p = 0.2). The post hoc nature of the subgroup analyses may limit their interpretation. Conclusions Sunitinib alone was noninferior compared with nephrectomy⬜sunitinib, suggesting that CN should not be considered SOC in patients with mRCC requiring systemic treatment. Certain subgroups, including patients with one IMDC risk factor, may still benefit from upfront CN. Patient summary We assessed the survival of patients with metastatic kidney cancer in a clinical trial. Patients treated with sunitinib on its own had the same survival as patients who had surgery before sunitinib treatment. We conclude that surgery may not be necessary for some patients with metastatic kidney cancer.
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- 2021
15. Expression of immune response biomarkers (PD‑L1, p16, CD3+ and CD8+ TILs) in recurrent head and neck squamous cell carcinoma within previously irradiated areas
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Julia Salleron, Jean‑Christophe Faivre, C. Pflumio, Gilles Dolivet, Xavier Sastre‑Garau, Jacques Thomas, Lionnel Geoffrois, and Christian Borel
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Male ,Cancer Research ,medicine.medical_treatment ,CD8-Positive T-Lymphocytes ,B7-H1 Antigen ,Lymphocytes, Tumor-Infiltrating ,Immune system ,PD-L1 ,Biomarkers, Tumor ,Tumor Microenvironment ,medicine ,Humans ,Aged ,Retrospective Studies ,Tumor microenvironment ,biology ,Squamous Cell Carcinoma of Head and Neck ,Tumor-infiltrating lymphocytes ,business.industry ,Head and neck cancer ,Cancer ,General Medicine ,Immunotherapy ,Middle Aged ,medicine.disease ,Head and neck squamous-cell carcinoma ,Oncology ,Head and Neck Neoplasms ,Cancer research ,biology.protein ,Radiotherapy, Adjuvant ,Neoplasm Recurrence, Local ,business - Abstract
The immune landscape of head and neck squamous cell carcinoma in pretreated areas remains poorly documented. We aimed to assess the tumor microenvironment for biomarkers of antitumor immune responses in tumors in previously irradiated areas compared with de novo tumors. This retrospective monocentric study analyzed 100 paraffin‑embedded surgical samples of invasive head and neck squamous cell carcinoma (oral cavity, oropharynx, larynx, hypopharynx) from patients who underwent surgery between January 2010 and November 2017. We compared the immune microenvironment in 50 de novo tumors and 50 tumors recurring within irradiated areas. We used immunohistochemistry to assess p16 status, CD3+/CD8+ tumor‑infiltrating lymphocytes (TILs), and programmed death‑ligand 1 (PD‑L1) expression on tumor and immune cells in stromal and intratumoral components. CD3+ TIL counts were significantly lower in intratumoral and stromal components (P=0.003 and P=0.020, respectively) in the irradiated area cohort; there was no significant difference between CD8+ TIL counts in the two cohorts. The percentage of tumors with PD‑L1+ tumor cells (tumor proportion score ≥1%) was significantly lower within the irradiated area cohort than the de novo cohort (56.0% vs. 86.0%, P
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- 2021
16. Real-world evidence of cabozantinib in patients with metastatic renal cell carcinoma: Results from the CABOREAL Early Access Program
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Anais Billard, Emeline Meriaux, Lionnel Geoffrois, Gwenaelle Gravis, Philippe Barthélémy, Brigitte Laguerre, Stéphane Oudard, Sylvain Ladoire, Laurence Albiges, Delphine Topart, Christine Chevreau, Valerie Perrot, Marine Gross-Goupil, Aude Flechon, Antoine Thiery-Vuillemin, Bernard Escudier, Jean Marc Tourani, Institut Gustave Roussy (IGR), Oncologie gynécologique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Centre Léon Bérard [Lyon], Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Claudius Regaud, CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), 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), 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 hospitalier universitaire de Poitiers (CHU Poitiers), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital JeanMinjoz, CHU Strasbourg, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), CRLCC Eugène Marquis (CRLCC), Ipsen [Boulogne Billancourt] (Ipsen), IPSEN, Hôpital Saint-André, NUNES, Jacques A, and Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)
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Male ,0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Cabozantinib ,Pyridines ,medicine.medical_treatment ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Renal cell carcinoma ,Internal medicine ,medicine ,Humans ,Anilides ,Neoplasm Metastasis ,Carcinoma, Renal Cell ,Aged ,Retrospective Studies ,Treatment patterns ,Proportional hazards model ,business.industry ,Receptor Protein-Tyrosine Kinases ,Retrospective cohort study ,Middle Aged ,medicine.disease ,French Early Access Program ,Nephrectomy ,Confidence interval ,Treatment Outcome ,Nivolumab ,030104 developmental biology ,Quartile ,chemistry ,030220 oncology & carcinogenesis ,Female ,business ,Body mass index - Abstract
International audience; Background: Real-world data on cabozantinib in metastatic renal cell carcinoma (mRCC) is limited. This study (CABOREAL) reports treatment patterns and outcomes for patients treated with cabozantinib through the French Early Access Program.Patients and methods: This multicentre (n = 26), observational, retrospective study enrolled patients with mRCC who had received ≥1 dose of cabozantinib. Overall survival (OS) was estimated using the Kaplan-Meier method; subgroups were compared using the log-rank test. A multiple Cox regression model assessed predictive factors of OS after cabozantinib initiation.Results: Four hundred and ten recruited patients started treatment between September 2016 and February 2018: the Eastern Cooperative Oncology Group Performance Status ≥2, 39.3%; poor International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk, 31.7%; 0-1, 2 and ≥3 previous treatment lines, 25.3%, 33.4% and 41.2%, respectively; bone metastases, 55.9%; brain metastases, 16.8%. Median (min-max) follow-up was 14.4 (0-30) months. Overall, 57.0% of patients had a dose reduction, 15.6% an alternative dose schedule. The median average daily dose was 40.0 mg. Median (quartile [Q]1-Q3) treatment duration was 7.6 (0.1-29.1) months, median OS was 14.4 months, and the 12-month OS rate was 56.5% (95% confidence interval: 51.5-61.2). Most patients (54.4%) received subsequent treatment. Predictive factors associated with longer OS were body mass index ≥25 kg/m2 (p = 0.0021), prior nephrectomy (p = 0.0109), favourable or intermediate IMDC risk (p < 0.0001) and cabozantinib initiation at 60 mg/day (p = 0.0486).Conclusions: In the largest real-world study to date, cabozantinib was effective in unselected, heavily pretreated patients with mRCC. Initiation at 60 mg/day was associated with improved outcomes. CLINICALTRIALS.
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- 2021
17. MBD4 deficiency is predictive of response to immune checkpoint inhibitors in metastatic uveal melanoma patients
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Mathilde Saint-Ghislain, Anne-Céline Derrien, Lionnel Geoffrois, Lauris Gastaud, Thierry Lesimple, Sylvie Negrier, Nicolas Penel, Jean-Emmanuel Kurtz, Yannick Le Corre, Caroline Dutriaux, Sophie Gardrat, Raymond Barnhill, Alexandre Matet, Nathalie Cassoux, Alexandre Houy, Toulsie Ramtohul, Vincent Servois, Pascale Mariani, Sophie Piperno-Neumann, Marc-Henri Stern, and Manuel Rodrigues
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Uveal Neoplasms ,Cancer Research ,Endodeoxyribonucleases ,Oncology ,Humans ,Neoplasm Metastasis ,Immune Checkpoint Inhibitors ,Melanoma ,Retrospective Studies - Abstract
MBD4 mutations have been reported in uveal melanomas, acute myeloid leukemias, colorectal adenocarcinomas, gliomas, and spiradenocarcinomas and cause a hypermutated phenotype. Although metastatic uveal melanomas (mUM) are usually resistant to immune checkpoint inhibitors (ICI), the first reported MBD4-mutated (MBD4m) patient responded to ICI, suggesting that MBD4 mutation may predict response to ICI.Retrospective cohort of mUM patients treated with ICI. MBD4 was sequenced in a subset of these patients.Three hundred mUM patients were included. Median follow-up was 17.3 months. Ten patients with an objective response and 20 cases with stable disease forgt;12 months were observed, corresponding to an objective response rate of 3.3% and a clinical benefit (i.e., responder patients and stable disease) rate of 10%. Of the 131 tumors sequenced for MBD4, five (3.8%) were mutated. MBD4 mutation was associated with a better objective response rate as three out of five MBD4m versus 4% of MBD4 wild-type patients responded (p lt; 0.001). Of these five responders, three presented progressive disease at 2.8, 13.9, and 22.3 months. Median PFS was 4.0 months in MBD4 wild-type and 22.3 months in MBD4m patients (HR = 0.22; p = 0.01). Median OS in MBD4def patients was unreached as compared to 16.6 months in MBD4pro (HR = 0.11; 95% CI: 0.02-0.86; log-rank p-test = 0.04; Fig. 2e).In mUM patients, MBD4 mutation is highly predictive for the response, PFS, and overall survival benefit to ICI. MBD4 could be a tissue-agnostic biomarker and should be sequenced in mUM, and other tumor types where MBD4 mutations are reported.
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- 2022
18. Debio 1143 and high-dose cisplatin chemoradiotherapy in high-risk locoregionally advanced squamous cell carcinoma of the head and neck: a double-blind, multicentre, randomised, phase 2 study
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Xu-Shan Sun, Yungan Tao, Christophe Le Tourneau, Yoann Pointreau, Christian Sire, Marie-Christine Kaminsky, Alexandre Coutte, Marc Alfonsi, Pierre Boisselier, Laurent Martin, Jessica Miroir, Jean-Francois Ramee, Jean-Pierre Delord, Florian Clatot, Frederic Rolland, Julie Villa, Nicolas Magne, Olgun Elicin, Elisabeta Gherga, France Nguyen, Cedrick Lafond, Guillaume Bera, Valentin Calugaru, Lionnel Geoffrois, Bruno Chauffert, Angela Zubel, Claudio Zanna, Silvano Brienza, Philippa Crompton, Elisabeth Rouits, Kathrin Gollmer, Sergio Szyldergemajn, and Jean Bourhis
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0301 basic medicine ,medicine.medical_specialty ,education.field_of_study ,business.industry ,Population ,Phases of clinical research ,medicine.disease ,Placebo ,Gastroenterology ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,Response Evaluation Criteria in Solid Tumors ,030220 oncology & carcinogenesis ,Internal medicine ,Mucositis ,medicine ,Clinical endpoint ,610 Medicine & health ,Adverse effect ,education ,business ,Chemoradiotherapy - Abstract
Summary Background Debio 1143 is an orally available antagonist of inhibitor of apoptosis proteins with the potential to enhance the antitumour activity of cisplatin and radiotherapy. The radiosensitising effect of Debio 1143 is mediated through caspase activation and TNF, IFNγ, CD8 T cell-dependent pathways. We aimed to investigate the efficacy and safety of Debio 1143 in combination with standard chemoradiotherapy in patients with high-risk locally advanced squamous cell carcinoma of the head and neck. Methods This double-blind, multicentre, randomised, phase 2 study by the French Head and Neck Radiotherapy Oncology Group (GORTEC) was run at 19 hospitals in France and Switzerland. Eligible patients were aged 18–75 years with locoregionally advanced, squamous cell carcinoma of the head and neck (characterised as non-metastatic, measurable stage III, IVa, or IVb [limited to T ≥2, N0–3, and M0] disease), Eastern Cooperative Oncology Group performance status of 0 or 1, a history of heavy tobacco smoking (>10 pack-years) with no previous or current treatment for invasive head and neck cancer, and no previous treatment with inhibitor of apoptosis protein antagonists. Patients were randomly assigned (1:1) to receive oral Debio 1143 (200 mg per day on days 1–14 of 21-day cycles, for three cycles) or oral placebo (20 mg/mL, administered at the same dosing schedule) using a stochastic minimisation technique according to node involvement and primary tumour site, and HPV-16 status in patients with an oropharyngeal primary tumour site. All patients received standard high-dose cisplatin chemoradiotherapy. The primary endpoint was the proportion of patients with locoregional control 18 months after chemoradiotherapy, analysed in the intention-to-treat population (primary analysis), and repeated in the per-protocol population. Responses were assessed according to Response Evaluation Criteria in Solid Tumors (version 1.1). This trial is registered with ClinicalTrials.gov , NCT02022098 , and is still active but not recruiting. Findings Between Jan 25, 2016, and April 24, 2017, 48 patients were randomly assigned to the Debio 1143 group and 48 to the placebo group (one patient in the placebo group did not receive the study drug and was not included in the safety analysis). Median duration of follow-up was 25·0 months (IQR 19·6–29·4) in the Debio 1143 group and 24·2 months (6·6–26·8) in the placebo group. Locoregional control 18 months after chemoradiotherapy was achieved in 26 (54%; 95% CI 39–69) of 48 patients in the Debio 1143 group versus 16 (33%; 20–48) of 48 patients in the placebo group (odds ratio 2·69 [95% CI 1·13–6·42], p=0·026). Grade 3 or worse adverse events were reported in 41 (85%) of 48 patients in the Debio 1143 group and in 41 (87%) of 47 patients in the placebo group. The most common grade 3–4 adverse events were dysphagia (in 24 [50%] patients in the Debio 1143 group vs ten [21%] in the placebo group), mucositis (in 15 [31%] vs ten [21%]), and anaemia (in 17 [35%] vs 11 [23%]). Serious treatment-emergent adverse events were recorded in 30 (63%) of 48 patients in the Debio 1143 group and 28 (60%) of 47 in the placebo group. In the placebo group, two (4%) deaths were due to adverse events (one multiple organ failure and one asphyxia; neither was considered to be related to treatment). No deaths due to adverse events occurred in the Debio 1143 group. Interpretation To our knowledge, this is the first treatment regimen to achieve superior efficacy in this disease setting against a high-dose cisplatin chemoradiotherapy comparator in a randomised trial. These findings suggest that inhibition of inhibitor of apoptosis proteins is a novel and promising approach in this poor prognostic population and warrant confirmation in a phase 3 study with the aim of expanding the therapeutic options for these patients. Funding Debiopharm.
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- 2020
19. Safety and Efficacy of Nivolumab in Brain Metastases From Renal Cell Carcinoma: Results of the GETUG-AFU 26 NIVOREN Multicenter Phase II Study
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Marine Gross-Goupil, Sylvie Chabaud, Mathieu Laramas, Gwenaelle Gravis, Frank Priou, Lionnel Geoffrois, Stéphane Culine, C. Dalban, Philippe Barthélémy, Marina Chenot, Stéphane Oudard, Frederic Rolland, Hakim Mahammedi, Florence Tantot, Delphine Borchiellini, Bernard Escudier, Nadine Houede, Sylvie Negrier, Sylvain Ladoire, Laurence Albiges, Bérengère Narciso, Florence Joly, Ronan Flippot, Christine Chevreau, Brigitte Laguerre, Elise Deluche, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), Centre Léon Bérard [Lyon], Centre Eugène Marquis (CRLCC), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), 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), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), UNICANCER, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Département de Biologie et pathologie des tumeurs [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, UFR des Sciences de Santé (Université de Bourgogne), Université de Bourgogne (UB), Département d'oncologie médicale [Centre Georges-François Leclerc], Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Département d'oncologie médicale, Institut Bergonié [Bordeaux], Service d'Oncologie médicale [CHU Limoges], CHU Limoges, Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, CHU Grenoble, Voies de Signalisation du Développement et du Stress Cellulaire dans les Cancers Digestifs et Urologiques, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Hopital Saint-Louis [AP-HP] (AP-HP), 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), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, and Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée)
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Adult ,Male ,0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Standard of care ,[SDV]Life Sciences [q-bio] ,Phases of clinical research ,03 medical and health sciences ,Antineoplastic Agents, Immunological ,0302 clinical medicine ,Text mining ,Renal cell carcinoma ,Internal medicine ,medicine ,Humans ,Carcinoma, Renal Cell ,Aged ,Brain Neoplasms ,business.industry ,Middle Aged ,medicine.disease ,3. Good health ,Editorial Commentary ,Clear cell renal cell carcinoma ,Nivolumab ,030104 developmental biology ,030220 oncology & carcinogenesis ,Female ,business - Abstract
PURPOSE Nivolumab is standard of care for patients with metastatic clear cell renal cell carcinoma (ccRCC) after failure of antiangiogenic therapies, but its activity on brain metastases from ccRCC remains unknown, because these patients were excluded from pivotal studies. We aimed to assess the activity of nivolumab in this population. METHODS The GETUG-AFU 26 NIVOREN phase II trial assessed the activity and safety of nivolumab in patients with metastatic ccRCC who failed vascular endothelial growth factor–directed therapies ( ClinicalTrials.gov identifier: NCT03013335 ). Patients with asymptomatic brain metastases were prospectively identified and underwent dedicated brain evaluation. Two cohorts were constituted: cohort A comprised patients with previously untreated brain metastases, and cohort B comprised patients whose brain metastases underwent prior therapy. The primary end point was intracranial response rate in cohort A. RESULTS Seventy-three patients with brain metastases were included: 39 in cohort A and 34 in cohort B. Intracranial response rate was 12% in cohort A; no objective response was reported in patients with brain lesions that were multiple or larger than 1 cm. Median intracranial progression-free survival was 2.7 months (95% CI, 2.3 to 4.6 months) in cohort A and 4.8 months (95% CI, 3.0 to 8.0 months) in cohort B, with adjusted hazard ratio of 2.04 (95% CI, 1.08 to 3.83). Overall survival rate at 12 months was 67% (95% CI, 49.6% to 79.1%) in cohort A and 59% (95% CI, 40.6% to 73.2%) in cohort B. Most patients in cohort A (72%) needed subsequent focal brain therapy. Nivolumab was well tolerated, with no unexpected toxicity. CONCLUSION Nivolumab activity is limited in patients with untreated brain metastases from ccRCC. Brain imaging and focal therapy should be considered before immune checkpoint inhibitors in patients with metastatic ccRCC.
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- 2019
20. Prise en charge des patients atteints de mélanome de stade III ou IV réséqué depuis l’arrivée de l’immunothérapie et de la thérapie ciblée en situation adjuvante en vie réelle
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Guido Bens, Ouidad Zehou, Marie-Thérèse Leccia, Amir Khammari, Laurent Misery, P. Celerier, Béatrice Crickx, Céleste Lebbé, S. Dalac-Rat, Thomas Jouary, Eve Maubec, S. Dalle, Florent Grange, Brigitte Dreno, Emilie Varey, Lionnel Geoffrois, and François Skowron
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Ocean Engineering ,Safety, Risk, Reliability and Quality - Published
- 2021
21. MBD4 deficiency is predictive of response to immune checkpoint inhibitors in metastatic uveal melanoma patients: A retrospective study
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Mathilde Saint-Ghislain, Lionnel Geoffrois, Lauris Gastaud, Thierry Lesimple, Sylvie Negrier, Nicolas Penel, Jean Emmanuel Kurtz, Yannick Le Corre, Caroline Dutriaux, Sophie Gardrat, Raymond Barnhill, Alexandre Matet, Nathalie Cassoux, Toulsie Ramtohul, Vincent Servois, Pascale Mariani, Sophie Piperno-Neumann, and Manuel Rodrigues
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Cancer Research ,Oncology - Abstract
e21601 Background: MBD4 encodes a glycosylase implicated in repair of lesions induced by DNA deamination and its inactivation in tumors is associated with a hypermutated phenotype. Uveal melanoma (UM) is a rare but aggressive form of melanoma carrying an extremely low mutation burden. Although metastatic UM (mUM) are usually resistant to immune checkpoint inhibitors (ICI), the first reported MBD4-mutated (MBD4m) patient responded to ICI, suggesting that MBD4 mutation may predict response to ICI. Since then, other MBD4-inactivated UMs, acute myeloid leukemias, colorectal adenocarcinomas, gliomas and spiradenocarcinoma cases have been reported. Methods: Retrospective cohort of mUM patients treated with ICI. MBD4 was sequenced in a subset of these patients. Results: Three hundred mUM patients were analyzed. Median follow-up was 17.3 months. Ten objective responses and 20 stable disease for > 12 months were observed, corresponding to an objective response rate of 3.3% and a clinical benefit (CB; i.e. responder patients and stable disease) rate of 10%. Median progression-free survivals (PFS) in patients without and with CB were 3.1 and 16.3 months, respectively (p < 0.0001). Of the 134 tumors sequenced for MBD4, five (3.7%) were mutated. MBD4 inactivation was associated with higher mutation burden (179 to 643 variants versus a median of 16 in MBD4 wild-type), better objective response rate as 60% of MBD4m versus 4% of MBD4-wild type patients responded (Fisher’s exact p-test = 0.0009). Median PFS was 4.0 months in MBD4-wild type and 22.3 months in MBD4m patients (HR = 0.22; p = 0.01). Median overall survival was 16.6 months in MBD4-wild type and unreached in MBD4m patients (HR = 0.11; p = 0.004). Conclusions: In mUM patients, MBD4 mutation is highly predictive for response to ICI, PFS and overall survival benefit. MBD4 could be a tissue-agnostic biomarker and should be sequenced in mUM and other tumor types where MBD4 mutations are reported.
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- 2022
22. Induction Chemotherapy Followed by Cetuximab Radiotherapy Is Not Superior to Concurrent Chemoradiotherapy for Head and Neck Carcinomas: Results of the GORTEC 2007-02 Phase III Randomized Trial
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Yoann Pointreau, Emmanuel Babin, Bernard Gery, Frederic Rolland, Joëlle Buffet, Cedric Khoury, Xu Shan Sun, Jean Bourhis, Pierre Guillet, Marc Alfonsi, Michel Lapeyre, Lionnel Geoffrois, Anne Rose Henry, François Guichard, Dominique De Raucourt, Ali Hasbini, Christian Sire, Marie Saliou, C. Tuchais, Pascal Garaud, Christian Borel, Philippe Maingon, Yungan Tao, Eric Jadaud, Jean-Marc Tourani, Ayman Zawadi, Nicolas Meert, Marie-Christine Kaminsky, Alexandre Coutte, Cédric Lafond, Laurent Martin, and Marie-Hélène Calais
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Standard of care ,Cetuximab ,business.industry ,medicine.medical_treatment ,Locally advanced ,Induction chemotherapy ,Concurrent chemoradiotherapy ,law.invention ,Radiation therapy ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Randomized controlled trial ,law ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Head and neck ,business ,medicine.drug - Abstract
Purpose Both concurrent chemoradiotherapy (CT-RT) and cetuximab radiotherapy (cetux-RT) have been established as the standard of care for the treatment of locally advanced squamous cell carcinoma of the head and neck. It was not known whether the addition of induction chemotherapy before cetux-RT could improve outcomes compared with standard of care CT-RT. Patients and Methods The current trial was restricted to patients with nonmetastatic N2b, N2c, or N3 squamous cell carcinoma of the head and neck and fit for taxotere, cisplatin, fluorouracil (TPF). Patients were randomly assigned to receive three cycles of TPF followed by cetux-RT versus concurrent carboplatin fluorouracil and RT as recommended in National Comprehensive Cancer Network guidelines. The trial was powered to detect a hazard ratio (HR) of 0.66 in favor of TPF plus cetux-RT for progression-free survival at 2 years. The inclusion of 180 patients per arm was needed to achieve 80% power at a two-sided significance level of .05. Results Between 2009 and 2013, 370 patients were included. All patients and tumors characteristics were well balanced between arms. There were more cases of grade 3 and 4 neutropenia in the induction arm, and the induction TPF was associated with 6.6% treatment-related deaths. With a median follow-up of 2.8 years, 2-year progression-free survival was not different between both arms (CT-RT, 0.38 v TPF + cetux-RT, 0.36; HR, 0.93 [95% CI, 0.73 to 1.20]; P = .58). HR was 0.98 (95% CI, 0.74 to 1.3; P = .90) for locoregional control and 1.12 (95% CI, 0.86 to 1.46; P = .39) for overall survival. These effects were observed regardless of p16 status. The rate of distant metastases was lower in the TPF arm (HR, 0.54 [95% CI, 0.30 to 0.99]; P = .05). Conclusion Induction TPF followed by cetux-RT did not improve outcomes compared with CT-RT in a population of patients with advanced cervical lymphadenopathy.
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- 2018
23. CN54 Impact of the app-based and nurse-led supportive care program AKO@dom on dose-intensity of oral targeted therapies in patients with metastatic renal cell cancer: A multicentric observational retrospective study
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Gabriel G. Malouf, Philippe Barthélémy, A. Fritsch, V. Gaillard, A. Lhuillier, Lionnel Geoffrois, C. Schuster, C. Bigot, L. Pierard, Delphine Borchiellini, and P. Trensz
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Oncology ,medicine.medical_specialty ,business.industry ,Retrospective cohort study ,Hematology ,Dose intensity ,Nurse led ,Internal medicine ,Medicine ,Observational study ,In patient ,business ,Care program ,Metastatic renal cell cancer - Published
- 2021
24. 670P Cabozantinib associated with concomitant radiotherapy or a bone targeted agent (multimodal approach, results from the CABOREAL study post-hoc analysis)
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Sylvain Ladoire, Valerie Perrot, L. Zara, Delphine Topart, E. Meriaux, B. Laguerre, Lionnel Geoffrois, Marine Gross-Goupil, Loic Mourey, Philippe Barthélémy, Aude Flechon, Antoine Thiery-Vuillemin, Stéphane Oudard, J-M. Tourani, Bernard Escudier, Laurence Albiges, and Gwenaelle Gravis
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Oncology ,medicine.medical_specialty ,Cabozantinib ,business.industry ,medicine.medical_treatment ,Multimodal therapy ,Hematology ,Radiation therapy ,chemistry.chemical_compound ,chemistry ,Concomitant ,Internal medicine ,Post-hoc analysis ,Medicine ,business - Published
- 2021
25. Association of adrenal metastases with outcomes in patients with metastatic clear cell renal cell carcinoma (mccRCC) treated with nivolumab in the GETUG-AFU-26 NIVOREN phase II trial
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Emilien Billon, Cécile Dalban, Stephane Oudard, Christine Chevreau, Brigitte Laguerre, Philippe Barthélémy, Delphine Borchiellini, Lionnel Geoffrois, Sylvie Negrier, Florence Joly, Antoine Thiery-Vuillemin, Marine Gross-Goupil, Frederic Rolland, Frank Priou, Hakim Mahammedi, Florence Tantot, Bernard Escudier, Sylvie Chabaud, Laurence Albiges, and Gwenaelle Gravis
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Cancer Research ,Oncology - Abstract
348 Background: Glandular metastases (GMs) (adrenal, pancreas, thyroid, ovary, breast, or prostate) are rare in mccRCC. Several studies have observed significantly longer overall survival (OS) for GM patients treated with anti-angiogenic therapy. This study assesses outcomes from mccRCC treated with nivolumab with or without GMs. Methods: The GETUG-AFU 26 NIVOREN, phase II trial assessed the activity and safety of nivolumab in pts with mccRCC who failed antiangiogenic therapies (NCT03013335). Pts were stratified in two subgroups according to the presence of at least one GM. Specific analyzes were performed for pancreatic and adrenal metastases. Primary endpoint was OS, secondary endpoint were progression free survival (PFS) and overall response rate (ORR). Results: Between February 2016 and July 2017, among 720 patients treated by nivolumab 217 patients had GM (151: adrenal and 86: pancreatic metastases). Clinical characteristics were comparable between the two subgroups except for IMDC poor subgroup (19% vs 28%) and for Furhman grade IV (13.5% vs 23.4%) for GM and non GM respectively. Median time between metastatic disease and nivolumab was 3.2 years (y) vs 2 y for GM and non GM respectively and 2.8 vs 2.1 y with or without adrenal metastasis. There was no statistical difference in outcomes between pts with or without GMs. However, pts with adrenal metastases had worse OS (12-months survival: 64% vs 71.1%; HR 1.51 (1.19-1.92)); shorter PFS (6-months survival: 27.2% vs 36.6%; HR 1.29 (1.07-1.57)) and lower ORR (12.5% [7.6%; 19.0%] vs 23.2% [19.8%; 27.0%]; p = 0.005) than non-adrenal metastases. Conversely, patients with pancreatic metastases had significantly longer overall survival (12-months survival: 82.3% vs 67.9%; HR 0.59 (0.40-0.85)) in univariate analysis compared to non-pancreatic metastases. In multivariate analysis, only adrenal metastasis remained associated with dismal prognosis (Table). Conclusions: Adrenal metastasis is an independent poor prognostic factor for response and survival in the GETUG-AFU 26 NIVOREN phase II trial. Limited activity with nivolumab is observed for patients with adrenal metastases from mccRCC without difference with previous anti angiogenic therapy. Molecular characterization could help to identify the angiogenic profile of adrenal metastases. Clinical trial information: NCT03013335. [Table: see text]
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- 2022
26. Efficacy and safety of nivolumab in renal cell carcinoma patients with BONE metastases: Results of the GETUG: AFU 26 nivoren multicenter phase II study
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Maud Velev, Cécile Dalban, Christine Chevreau, Gwenaelle Gravis, Sylvie Negrier, Brigitte Laguerre, Marine Gross-Goupil, Sylvain Ladoire, Victoria Ferrari, Lionnel Geoffrois, Hubert Curcio, Frank Priou, Quentin Dominique Thomas, Cécile Mione, Philippe Barthélémy, Florence Tantot, Bernard Escudier, Sylvie Chabaud, Laurence Albiges, and Constance Thibault
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Cancer Research ,Oncology - Abstract
342 Background: Bone metastases (BM) in renal cell carcinoma (RCC) are associated with a poor prognosis based on retrospective studies in which patients were treated with antiangiogenic agents. Since the development of immune checkpoint inhibitors, few data are available regarding the prognosis impact of BM or the efficacy and safety of checkpoint inhibitors in patients with bones metastatic RCC. GETUG-AFU26-NIVOREN (NIVOREN) is a French multicenter prospective study in which patients were treated with nivolumab after failure of one or more antiangiogenic tyrosine kinase inhibitors. We therefore aim to evaluate the impact of BM on prognosis, and the efficacy and safety of nivolumab in patients with BM enrolled in NIVOREN trial. Methods: All adult patients with BM at inclusion were included in our study. The primary endpoint of this ancillary study was overall survival (OS). Secondary endpoints were progression-free survival (PFS), objective response rate (ORR), safety, and skeletal-related events (SRE) in patients with BM. Clinical data were collected prospectively, except for SRE data which were collected retrospectively in a complementary consent report form. Results: Among 720 patients treated with nivolumab in the NIVOREN study, 194 had BM at inclusion. After a median follow-up of 23.9 months, the median OS was 17.9 months in patients with BM versus 26.1 months in patients without BM (HR = 1.42 CI95% [1.13-1.79], p = 0.0023). After adjustment on sex, age, IMDC group and line of treatments, the difference was not significant (HR = 1.24, CI95% [0.98-1.56], p = 0.0707). The median PFS was shorter in patients with BM even after adjustment (2.8 versus 4.6 months, HR = 1.30 CI95% [1.08-1.56]), as well as the ORR (14.8% versus 23.3%). The safety profile was similar between patients with or without BM at inclusion. The incidence of SRE in the BM population was 36% during the treatment period with nivolumab. A post-hoc analysis evaluating the impact of bone-targeting agents in association with nivolumab on SRE incidence was performed. There was a statistically significant benefit in patients treated with bone-targeting agents on the incidence of SRE (OR = 0.367, CI95% [0.151-0.895], p = 0.0276). Conclusions: Nivolumab is associated with shorter OS, PFS, and lower ORR in patients with BM. Our study confirms, in the era of immunotherapy that patients with BM are associated with poorer prognosis and suggests that association with bone-targeting agents decreases the incidence of SRE. Clinical trial information: 2015-004117-24.
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- 2022
27. Debio 1143 Combined with Concurrent High-Dose Cisplatin Chemoradiotherapy in Patients with High-Risk Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck: A Double Blind, Randomised, Placebo Controlled, Multicentre Phase 2 Study (GORTEC 2015-03)
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Xu-Shan Sun, Yungan Tao, Christophe Le Tourneau, Yoann Pointreau, Christian Sire, Marie-Christine Kaminsky, Alexandre Coutte, Marc Alfonsi, Pierre Boisselier, Laurent Martin, Jessica Miroir, Jean-Francois Ramee, Jean-Pierre Delord, Florian Clatot, Frederic Rolland, Julie Villa, Nicolas Magne, Olgun Elicin, Elisabeta Gherga, France Nguyen, Cédrik Lafond, Guillaume Bera, Valentin Calugaru, Lionnel Geoffrois, Bruno Chauffert, Angela Zubel, Claudio Zanna, Philippa Crompton, Elisabeth Rouits, Kathrin Gollmer, Sergio Szyldergemajn, and Jean Bourhis
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- 2020
28. Cetuximab, Docetaxel and Cisplatin as First-Line Treatment in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Results of the GORTEC 2014-01 TPExtreme Randomized Trial
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Joël Guigay, Anne Aupérin, Jerome Fayette, Esma Saada-Bouzid, Cédrik Lafond, Miren Taberna, Lionnel Geoffrois, Laurent Martin, Olivier Capitain, Didier Cupissol, Hélène Castanie, Damien Vansteene, Philippe Schafhausen, Alison Johnson, Caroline Even, Christian Sire, Sophie Duplomb, Camille Evrard, Jean-Pierre Delord, Brigitte Laguerre, Sylvie Zanetta, Cécile Chevassus, Aldéric Fraslin, Fanny Louat, Laura Sinigaglia, Ulrich Keilholz, Jean Bourhis, Ricard Mesia, and GORTEC, AIO, TTCC, UniCancer H& Group
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medicine.medical_specialty ,Performance status ,Cetuximab ,business.industry ,Head and neck cancer ,medicine.disease ,law.invention ,Regimen ,Randomized controlled trial ,Quality of life ,law ,Internal medicine ,medicine ,Clinical endpoint ,Adverse effect ,business ,medicine.drug - Abstract
Background: After promising results from TPEx phase II trial in first line recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC), this trial compared the TPEx regimen (docetaxel-platinum-cetuximab) to the standard EXTREME regimen. Methods: Patients with R/M HNSCC unsuitable for curative treatment were randomized between TPEx (four cycles docetaxel-cisplatin-cetuximab followed by cetuximab maintenance 500 mg/m² every two weeks) and EXTREME (six cycles 5FU-cisplatin-cetuximab followed by weekly cetuximab 250 mg/m² maintenance). Main inclusion criteria were patients fit for cisplatin, performance status (PS) ≤1, creatinine clearance >60ml/min, and age
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- 2020
29. Are immune checkpoint inhibitors a valid option for papillary renal cell carcinoma? A multicentre retrospective study
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Sylvie Negrier, Alain Ravaud, Philippe Barthélémy, Olivier Huillard, Valérie Seegers, Carolina Saldana, Delphine Borchiellini, Manon de Vries-Brilland, Bernard Escudier, Sylvain Ladoire, Elouen Boughalem, Constance Thibault, Gwenaelle Gravis, Antoine Thiery-Vuillemin, Lionnel Geoffrois, Laurence Albiges, Christine Chevreau, Marine Gross-Goupil, and Benoit Beuselinck
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0301 basic medicine ,Oncology ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Drug-Related Side Effects and Adverse Reactions ,Population ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Antineoplastic Agents, Immunological ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Adverse effect ,education ,Carcinoma, Renal Cell ,Immune Checkpoint Inhibitors ,Aged ,Retrospective Studies ,Aged, 80 and over ,education.field_of_study ,Papillary renal cell carcinomas ,business.industry ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Survival Analysis ,Immune checkpoint ,Kidney Neoplasms ,Discontinuation ,Clinical trial ,030104 developmental biology ,Treatment Outcome ,030220 oncology & carcinogenesis ,Female ,business ,Progressive disease - Abstract
Background Papillary renal cell carcinoma (pRCC) is the most common non-clear cell RCC (nccRCC). Pivotal studies evaluating immune checkpoint inhibitors mostly excluded nccRCC. The aim of this retrospective and multicentre study was to evaluate the activity of programmed death-1 (PD-1)/ programmed death-ligand 1 (PD-L1) inhibitors specifically in metastatic pRCC. Methods The primary end-point 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 01/2019, 57 patients with pRCC were included. Histology included 16 (28%) type 1 pRCC, 34 (60%) type 2 pRCC and 7 (12%) unclassified pRCC. Treatment with immune checkpoint inhibitors was used in the first-line setting in 4 patients (7%), in the second-line setting in 32 patients (56%) and in the third-line setting or more in 21 patients (37%). With a median follow-up of 12 months (95% confidence interval [CI]: 9.9–21.0), the median TTF was 3.1 months (95% CI: 2.7–5.0). Among the 55 patients evaluable for ORR, best response was complete response/partial response in 6 patients (11%), stable disease in 18 patients (33%) and progressive disease in 31 patients (56%). The median OS was 14.6 months (95% CI: 9.0- not reached). TRAEs of grade III–IV were noted in 6 patients (10%) leading to treatment discontinuation, and no grade V TRAEs were observed. Conclusion PD-1/PD-L1 inhibitors exhibit limited activity as monotherapy in this pRCC population, which remains an unmet need. Our findings underline the need for further prospective clinical trials evaluating immune checkpoint inhibitor combinations in patients with pRCC.
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- 2019
30. Nephrectomy After Complete Response to Immune Checkpoint Inhibitors for Metastatic Renal Cell Carcinoma: A New Surgical Challenge?
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Vincenzo di Nunno, Karim Bensalah, Louis Leblanc, Sylvain Ladoire, Jochen Walz, Pierre Werle, Pierre Bigot, Gwenaelle Gravis, Philippe Barthélémy, Laurence Albiges, Lionnel Geoffrois, Antoine Thiery-Vuillemin, Géraldine Pignot, L. Balssa, and Hervé Lang
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business.industry ,Urology ,Immune checkpoint inhibitors ,medicine.medical_treatment ,Remission Induction ,medicine.disease ,Combined Modality Therapy ,Nephrectomy ,Kidney Neoplasms ,Renal cell carcinoma ,Cancer research ,Medicine ,Feasibility Studies ,Humans ,business ,Carcinoma, Renal Cell ,Immune Checkpoint Inhibitors ,Complete response ,Retrospective Studies - Published
- 2019
31. Patterns of relapse in poor-prognosis germ-cell tumours in the GETUG 13 trial: Implications for assessment of brain metastases
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Anne-Laure Martin, Gwenaelle Gravis, J. P. Malhaire, G. Le Teuff, Frederic Rolland, J.-C. Eymard, M. Reckova, F. Journeau, Aude Flechon, Lance C. Pagliaro, Muriel Habibian, Jozef Mardiak, Stéphane Culine, Karim Fizazi, Christopher J. Logothetis, Yohann Loriot, P. Kerbrat, Christine Chevreau, Guilhem Roubaud, A. Laplanche, Remy Delva, Claude Linassier, Christine Theodore, and Lionnel Geoffrois
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Male ,0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Poor prognosis ,Time Factors ,medicine.medical_treatment ,Radiography ,Kaplan-Meier Estimate ,Bleomycin ,Disease-Free Survival ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Testicular Neoplasms ,Risk Factors ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Multicenter Studies as Topic ,Etoposide ,Proportional Hazards Models ,Retrospective Studies ,Cisplatin ,Chemotherapy ,Brain Neoplasms ,business.industry ,Neoplasms, Germ Cell and Embryonal ,Magnetic Resonance Imaging ,United States ,Surgery ,Regimen ,Treatment Outcome ,030104 developmental biology ,medicine.anatomical_structure ,Clinical Trials, Phase III as Topic ,chemistry ,030220 oncology & carcinogenesis ,Disease Progression ,France ,Tomography, X-Ray Computed ,business ,Germ cell ,medicine.drug - Abstract
Background The GETUG 13 phase III trial tested personalised chemotherapy based on tumour marker decline in patients with poor-prognosis germ-cell tumour (GCT) and demonstrated that a dose-dense regimen improves progression-free survival in patients with an unfavourable decline. We investigated the pattern of relapse for patients included in GETUG 13. Methods We conducted an analysis of relapse events in patients from GETUG 13. Baseline procedures before inclusion in the trial comprised a thoraco-abdomino-pelvic computed tomography scan and a magnetic resonance imaging of the brain. Results With a median follow-up of 4.1 years (0.3; 8.8 years), a progression event was observed in 109/254 patients (43%). First event consisted in a marker progression only in 47 patients (43%), a radiographic progression only in 35 patients (32%), a mix progression on both markers and imaging in 12 patients (11%) and death in 15 patients (14%). In patients with radiographic progression only, brain was the predominant site (n = 19/35, 54%). Among patients with unfavourable decline who experienced a radiographic progression (as first and subsequent progression event, n = 58), brain was a site of progression in 28 patients (48%): 12/30 (40%) in patients treated with cisplatin, bleomycin and etoposide and 16/28 (57%) in those treated with dose-dense chemotherapy. Conclusions Brain metastases develop often, early and frequently as the only site of relapse in the course of poor-prognosis GCT. This raises the question of early detection and optimal treatment of brain metastases in these patients, e.g. by integrating a systematic brain MRI after 2–3 months of chemotherapy.
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- 2017
32. P07.04 Primary Lung Cancers in Patients With Head and Neck Cancer: Experience of a French Institution
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J. Salleron, R. Mastronicola, M. Kaminsky, S. Cortses, Gilles Dolivet, E. Beulque, Jean-Christophe Faivre, Lionnel Geoffrois, and Christelle Clément-Duchêne
- Subjects
Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Lung ,medicine.anatomical_structure ,Oncology ,business.industry ,General surgery ,Head and neck cancer ,medicine ,In patient ,medicine.disease ,business - Published
- 2021
33. 697P Impact of β-blockers (BB) on outcomes of metastatic renal cell carcinoma (mRCC) patients treated with nivolumab (N)
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Stéphane Oudard, Frederic Rolland, Marine Gross-Goupil, Bernard Escudier, C. Alves Costa Silva, Lionnel Geoffrois, Gwenaelle Gravis, Lisa Derosa, Sylvie Negrier, B. Laguerre, C. Dalban, Delphine Borchiellini, Christine Chevreau, Sylvain Ladoire, Florence Joly, Laurence Albiges, Emeline Colomba, Antoine Thiery-Vuillemin, Florence Tantot, and Philippe Barthélémy
- Subjects
Oncology ,medicine.medical_specialty ,Renal cell carcinoma ,business.industry ,Internal medicine ,medicine ,Hematology ,Nivolumab ,medicine.disease ,business - Published
- 2021
34. 713P Assessment of bleomycin pulmonary toxicity in men with poor-prognosis non-seminomatous germ-cell tumors treated in the GETUG 13 phase III trial
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Jozef Mardiak, Remy Delva, N. Naoun, J. P. Malhaire, Frederic Rolland, G. Le Teuff, S. Nenan, Stéphane Culine, Christine Chevreau, Lionnel Geoffrois, J.-C. Eymard, Gwenaelle Gravis, M. Reckova, Karim Fizazi, P. Kerbrat, Aude Flechon, Luigi Pagliaro, Guilhem Roubaud, Christine Theodore, and Claude Linassier
- Subjects
Poor prognosis ,chemistry.chemical_compound ,Oncology ,chemistry ,Pulmonary toxicity ,business.industry ,Cancer research ,medicine ,Hematology ,Germ cell tumors ,medicine.disease ,business ,Bleomycin - Published
- 2021
35. Prognosis impact of serous metastases (SMs) in clear cell renal cell carcinoma patients in the GETUG-AFU-26 NIVOREN phase II trial
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Sylvie Negrier, Bernard Escudier, Sylvain Ladoire, Stéphane Oudard, Florian Bardet, Laurence Albiges, Christine Chevreau, Marine Gross-Goupil, Gwenaelle Gravis, Cécile Dalban, Jean Marc Ferrero, Brigitte Laguerre, Antoine Thiery-Vuillemin, Lionnel Geoffrois, Florence Tantot, Bérangère Narciso, Hakim Mahammedi, and Philippe Barthélémy
- Subjects
Oncology ,Cancer Research ,Serous fluid ,Clear cell renal cell carcinoma ,medicine.medical_specialty ,Standard of care ,business.industry ,Internal medicine ,medicine ,Nivolumab ,medicine.disease ,business - Abstract
e16566 Background: Nivolumab monotherapy (N) is a standard of care for patients with metastatic clear cell renal cell carcinoma (ccRCC) after failure of antiangiogenic therapies. IMDC criteria is the established prognostic model in anyline of systemic treatment including with N. While liver, bone and brain have been reported to convey a dismal prognosis, little is known about the pejorative prognostic impact of serous metastatic sites (pleura, peritoneum, pericardium) in patients receiving anti-PD (L) -1 treatment. Methods: We aimed to assess survival, and activity of N in patients included in the GETUG-AFU 26 NIVOREN phase II prospective trial ( NCT03013335 ), according to serous metastases (SMs). Results: Overall, 720 patients with metastatic ccRCC, and treated with N. Baseline RECIST metastases data were available for 708 patients included in this analysis. Among them, 142 (20%) had SMs (pleura, n=91 ; peritoneum, n=50 ; pericardium, n=1). Median PFS (4.5 vs 2.6 mo ; HR :1.31 ; p=0.0079), and OS (26.1 vs 15 mo ; HR :1.67 ; p
- Published
- 2021
36. Interim analysis of IMMUNEBOOST-HPV: A multicenter, randomized, open label, phase II study evaluating the feasibility, and tolerance of neoadjuvant nivolumab in high-risk HPV driven oropharynx cancer
- Author
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Haitham Mirghani, Caroline Even, Alicia Larive, Jerome Fayette, Karen Benezery, Florian Clatot, Lionnel Geoffrois, Yungan Tao, France Nguyen, Emmanuelle Fabiano, Sarah Kreps, Eve Marie Neidhardt, Florence Garic, Anne Auperin, and Pierre Blanchard
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Phases of clinical research ,Cancer ,Immunotherapy ,Favorable prognosis ,Interim analysis ,medicine.disease ,High risk hpv ,Internal medicine ,Medicine ,Open label ,Nivolumab ,business - Abstract
6037 Background: Among HPV-positive Oropharyngeal Cancer (OPC) patients (pts), some has a less favorable prognosis (T4, N2/N3, smokers >10 pack-year [p/y]). We assume that neoadjuvant immunotherapy might improve their oncological outcomes, so we tested nivolumab (N) prior to ChemoRadiaTion (CRT). Methods: The study population is restricted to HPV positive OPC pts (both p16+ & HPV-DNA+) with advanced disease (T4, N2/N3) or a smoking history >10 p/y. Pts were randomly allocated 1:2 to receive either cisplatin-based CRT (n=20) or 2 cycles of N 240 mg followed by CRT (n=41). The Primary Endpoint (PE) is the rate of pts who can receive Full Treatment in Due Time (FTDT), according to these criteria: a) 2 N infusions on day 1 and on day 14-16 b) CRT started between days 28-37 after the 1st N infusion c) No RT break ≥1 week d) RT dose received >95% of theoretical dose e) Cisplatin dose received ≥200 mg/m² To achieve FTDT, all criteria are required in the Experimental Arm (EA) while only criteria c), d), and e) are required in the Control Arm (CA). In the EA, the trial was designed in 2 steps, with FTDT rate of 88% considered as inacceptable versus an alternative of 98%, a type I error of 0.10, and a type 2 error of 0.08. As per protocol, patient accrual was temporarily suspended after inclusion of 19 pts in the EA (1st step) and results were reviewed by an Independent Data Monitoring Committee (IDMC). To resume pts’ inclusion, FTDT had to be achieved in 18 pts in the EA. Results: From 07/2019 to 09/2020, 30 pts were enrolled including 11 in the CA (demographics are summarized in table). 2 pts in the EA did not reach the PE. For the 1st patient, the cisplatin dose was 2 due to grade 1 hearing loss and grade 2 tinnitus (1st cycle: 100 mg/m2, 2nd cycle: 80 mg/m2, no 3rd cycle). For the 2nd patient, CRT began at D38 due to logistical issues (maintenance of RT devices). As this delay was unrelated to N or to patient's condition, the IDMC considered that the inclusions could resume for the 2nd step. 7 N-related Adverse Events (AE) were reported in 4 pts including 3 serious AE (ankylosing spondylitis flare-up, colitis, diabetic ketoacidosis). Conclusions: Neoadjuvant N before CRT seems feasible for the treatment of OPC pts. The trial has reopened to inclusion as recommended by the IDMC. Clinical trial information: NCT03838263. [Table: see text]
- Published
- 2021
37. Nephrectomy after response to immune checkpoint inhibitors for metastatic renal cell carcinoma (mRCC): A surgical challenge allowing favorable oncological outcomes
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L. Balssa, Laurence Albiges, Friederike Schlurmann, Ophelie Cassuto, Géraldine Pignot, Philippe Barthélémy, Jean-Christophe Bernhard, Herve Lang, Alexandre Ingels, Antoine Thiery-Vuillemin, Guilhem Roubaud, Delphine Borchiellini, Victor Gaillard, Bastien Parier, Jochen Walz, Karim Bensalah, Pierre Bigot, Lionnel Geoffrois, Gwenaelle Gravis, and Sylvain Ladoire
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Oncology ,Cancer Research ,medicine.medical_specialty ,Renal cell carcinoma ,business.industry ,Immune checkpoint inhibitors ,medicine.medical_treatment ,Internal medicine ,medicine ,medicine.disease ,business ,Nephrectomy - Abstract
e16557 Background: In the current era of Immune checkpoint inhibitors (ICI), the role and timing of nephrectomy is still unknown. We aimed to evaluate the oncological outcomes of patients with metastatic renal cell carcinoma (mRCC) managed with nephrectomy for residual disease after complete response (CR) or major partial response (mPR defined as > 80%) on metastatic sites following ICI. Methods: Patients who underwent nephrectomy after prior ICI between 2015 and 2020 were retrospectively included and clinicopathological data were reviewed. Perioperative data, postoperative complications, toxicities related to ICI, continuation or discontinuation of systemic treatment following surgery, and 1-year oncological outcomes were recorded. Results: Twenty-five patients without initial cytoreductive nephrectomy at diagnosis underwent delayed nephrectomy after long ICI administration because of CR (or mPR) on metastatic sites. Median age was 62 years [38-79]. 88% of patients had clear cell RCC on the initial biopsy. IMDC prognostic group was intermediate (80%) or poor (20%). ICI was administered as first-line therapy in 56.0% of cases and as second-line option after TKI in 44.0% of cases. Treatments regimens were: nivolumab + ipilimumab (n = 12), nivolumab + tivozanib (n = 2) or nivolumab alone (n = 11). The mean duration of ICI treatment was 11.8 months (range: 3-38 months) and the mean number of cycles was 19 (range: 6-75). Twelve patients had a CR on metastatic sites while 13 patients had a mPR ( > 80%). Overall, 64% of patients experienced toxicities related to ICI treatment. Median operative time was 210 minutes [90-345] and mean blood loss was 558 cc [40-4000]. In 80.0% of cases, surgeons experienced difficulties in finding dissection plans due to adhesions and/or inflammatory infiltration. The 30-day Clavien-Dindo postoperative complication rate was 36.0%, including 1 surgery-related death. Pathological report showed lymphocyte and/or macrophage infiltration in 60% of cases and complete pathological response (pT0) in 3 cases (12%). After a mean follow-up of 19.4 months, 79.2% of the patients were free from progression and 70.8% free from systemic treatment. The recurrence-free survival (RFS) and overall survival (OS) at 1 year were 79.5% and 89.8% respectively. CR on metastatic sites was significantly associated with good RFS compared to mPR (1-year RFS = 100% vs. 56.8%, median RFS = 21.6 vs. 4.25 months, p = 0.006) while the duration of IO treatment exposure was not. Conclusions: Nephrectomy following ICI for mRCC can be a difficult procedure. However, it may provide good long-term RFS, with systemic treatment discontinuation following surgery in most cases. This strategy may be offered in well-selected patients, especially in case of CR on metastatic sites before surgery.
- Published
- 2021
38. 752P Updated data from the NORSE trial of erdafitinib (ERDA) plus cetrelimab (CET) in patients (pts) with metastatic or locally advanced urothelial carcinoma (mUC) and specific fibroblast growth factor receptor (FGFR) alterations
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Luc Dirix, Remy Delva, Victor Moreno, A.P. Lykov, Begoña Mellado, Y. Loriot, Sergei Varlamov, Arlene O. Siefker-Radtke, Sydney Akapame, A. Semenov, Salvatore Siena, S. Mosher, Carmen Beato, Anne OHagan, Ignacio Duran, M.A. Climent Duran, Scott T. Tagawa, T.W. Kang, M. Tammaro, and Lionnel Geoffrois
- Subjects
Oncology ,Erdafitinib ,Fibroblast growth factor receptor ,business.industry ,Locally advanced ,Cancer research ,Medicine ,In patient ,Hematology ,business ,Urothelial carcinoma - Published
- 2020
39. 732P Cabozantinib in non-clear cell metastatic renal cell carcinoma and sarcomatoid renal cell carcinoma: Real-world data from the CABOREAL study
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Laurence Albiges, Jean-Marc Tourani, B. Laguerre, G. Gravis, Bernard Escudier, Stéphane Oudard, Philippe Barthélémy, Sylvain Ladoire, Christine Chevreau, Valerie Perrot, Delphine Topart, Lionnel Geoffrois, Marine Gross-Goupil, Aude Flechon, E. Meriaux, R. Bourouina, and Antoine Thiery-Vuillemin
- Subjects
chemistry.chemical_compound ,Oncology ,Cabozantinib ,chemistry ,business.industry ,Sarcomatoid Renal Cell Carcinoma ,Cancer research ,Medicine ,Hematology ,Clear-cell metastatic renal cell carcinoma ,business ,Real world data - Published
- 2020
40. 712P Primary tumour response in patients treated with nivolumab for metastatic renal cell carcinoma (mRCC): Results of the GETUG-AFU 26 NIVOREN trial
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Christine Chevreau, Elise Deluche, Frederic Rolland, J. Courcier, C. Dalban, Sylvie Negrier, G. Gravis Mescam, Philippe Barthélémy, B. Laguerre, Florence Joly, Florence Tantot, Delphine Topart, Bernard Escudier, Lionnel Geoffrois, Ronan Flippot, Stéphane Oudard, Laurence Albiges, Stéphane Culine, Sylvain Ladoire, and Hakim Mahammedi
- Subjects
Oncology ,medicine.medical_specialty ,business.industry ,Renal cell carcinoma ,Internal medicine ,Medicine ,In patient ,Hematology ,Nivolumab ,business ,medicine.disease ,Tumour response - Published
- 2020
41. 722P Cabozantinib in elderly patients: Results from a subanalysis of the CABOREAL study
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E. Meriaux, Laurence Albiges, B. Laguerre, R. Bourouina, Antoine Thiery-Vuillemin, Lionnel Geoffrois, Loic Mourey, Marine Gross-Goupil, Aude Flechon, Stéphane Oudard, G. Gravis, Bernard Escudier, Delphine Topart, Philippe Barthélémy, Jean-Marc Tourani, Sylvain Ladoire, and Valerie Perrot
- Subjects
Oncology ,medicine.medical_specialty ,chemistry.chemical_compound ,Cabozantinib ,chemistry ,business.industry ,Internal medicine ,medicine ,Hematology ,business - Published
- 2020
42. A double-blind phase III trial of immunomodulating nutritional formula during adjuvant chemoradiotherapy in head and neck cancer patients: IMPATOX
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Pierre Senesse, Didier Cupissol, S. Thezenas, Christian Sire, Neck Oncology, Sandrine Lavau-Denes, Chloé Janiszewski, Hélène de Forges, Muriel Garcia-Ramirez, Olivier Gallocher, Marc Alfonsi, Lionnel Geoffrois, Marie-Christine Kaminsky, and P. Boisselier
- Subjects
0301 basic medicine ,Adult ,Male ,medicine.medical_specialty ,Medicine (miscellaneous) ,Gastroenterology ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Double-Blind Method ,Internal medicine ,Multicenter trial ,medicine ,Mucositis ,Humans ,Immunologic Factors ,Progression-free survival ,Aged ,Food, Formulated ,030109 nutrition & dietetics ,Nutrition and Dietetics ,Intention-to-treat analysis ,business.industry ,Chemoradiotherapy, Adjuvant ,Middle Aged ,medicine.disease ,Head and neck squamous-cell carcinoma ,Chemotherapy regimen ,Head and Neck Neoplasms ,030220 oncology & carcinogenesis ,Concomitant ,Dietary Supplements ,Female ,business ,Chemoradiotherapy - Abstract
Background In a previous phase II study an immunonutrient supplement was found to reduce severe acute toxicities for head and neck squamous cell cancer (HNSCC) patients treated with concomitant cisplatin and radiotherapy. Objectives The primary objective of the present study was to evaluate efficacy of the same immunonutrient supplement on severe mucositis. Secondary objectives included tolerance, compliance to oral supplementation, chemotherapy interruptions and delays, quality of life, and progression-free survival (PFS) and overall survival (OS) at 1, 2, and 3 y. Methods Between November 2009 and June 2013, 180 HNSCC patients eligible for adjuvant chemotherapy after surgery with curative intent were included in our double-blind phase III multicenter trial. They were assigned to receive oral supplementation (3 sachets/d) of either a formula enriched with l-arginine and omega-3 (n-3) fatty and ribonucleic acids (experimental arm), or an isocaloric isonitrogenous control (control arm), for 5 d before each of 3 cycles of cisplatin. Intention-to-treat (ITT) and per-protocol (PP) analyses were undertaken, along with subgroup analyses of ≥75% compliant patients, to compare the incidence of acute mucositis (Radiation Therapy Oncology Group and WHO scales) and 36-mo survival. Results At 1 mo after terminating chemoradiotherapy (CRT), no differences were observed in the incidence of grade 3-4 mucositis between treatment groups, in the ITT, PP (172 patients), and subgroup (≥75% compliance, n = 112) analyses. The immunomodulating supplement did not significantly improve survival in the ITT and PP analyses at 3 y after CRT. Among ≥75% compliant patients, however, OS at 3 y was significantly improved in the immunomodulating formula group (81%; 95% CI: 67%, 89%) compared with controls (61%; 95% CI: 46%, 73%; P = 0.034), as well as PFS (73%; 95% CI: 58%, 83% compared with 50%; 95% CI: 36%, 63%; P = 0.012). Conclusions Although this immunomodulating formula failed to reduce severe mucositis during CRT, the findings suggest that the long-term survival of compliant HNSCC patients was improved.This trial was registered at clinicaltrials.gov as NCT01149642.
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- 2019
43. Unilateral or bilateral irradiation in cervical lymph node metastases of unknown primary? A retrospective cohort study
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J. Khalifa, C. Pflumio, Shakeel Sumodhee, Matthieu Caubet, Ludivine Catteau, Xu Shan Sun, Amel Rehailia-Blanchard, A. Beddok, Vincent Roth, I. Troussier, Joël Castelli, Marco Krengli, Charles Dupin, Nicolas Blanchard, Valentin Calugaru, Jean-Christophe Faivre, Yoann Pointreau, Juliette Thariat, Julia Salleron, Jessica Miroir, Mélanie Doré, Edouard Romano, Paul Giraud, Samir H. Patel, S. Servagi-Vernat, Alexandre Coutte, René-Jean Bensadoun, Claire Petit, Lionnel Geoffrois, Yungan Tao, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Hôpital Nord Franche-Comté [Hôpital de Trévenans] (HNFC), Institut Gustave Roussy (IGR), Service de Radiothérapie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Institut Jean Godinot [Reims], CRLCC Eugène Marquis (CRLCC), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), CHU Amiens-Picardie, Service d'Oncologie radiothérapie [Clinique Victor Hugo], Clinique Victor Hugo [Le Mans], Mayo Clinic, CHU Saint-Etienne, Centre hospitalier universitaire de Poitiers (CHU Poitiers), EASY CRF : la recherche clinique en ligne, and ARCHADE (Advanced Resource Centre for HADrontherapy in Europe)
- Subjects
Male ,0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,Neck dissection ,Head and neck neoplasms ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Cervical lymphadenopathy ,Neoplasms ,Chemotherapy ,Radiotherapy ,Unknown primary ,Carcinoma ,Humans ,Medicine ,Cumulative incidence ,Lymph node ,Aged ,Retrospective Studies ,Squamous Cell Carcinoma of Head and Neck ,business.industry ,Retrospective cohort study ,Middle Aged ,medicine.disease ,3. Good health ,Surgery ,Radiation therapy ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,Lymphatic Metastasis ,030220 oncology & carcinogenesis ,Concomitant ,Neoplasms, Unknown Primary ,Female ,Lymph Nodes ,medicine.symptom ,business - Abstract
Patients with cervical lymphadenopathy of unknown primary carcinoma (CUP) usually undergo neck dissection and irradiation. There is an ongoing controversy regarding the extent of nodal and mucosal volumes to be irradiated. We assessed outcomes after bilateral or unilateral nodal irradiation.This retrospective multicentre study included patients with CUP and squamous cellular carcinoma who underwent radiotherapy (RT) between 2000 and 2015.Of 350 patients, 74.5% had unilateral disease and 25.5% had bilateral disease. Of 297 patients with available data on disease and irradiation sides, 61 (20.5%) patients had unilateral disease and unilateral irradiation, 155 (52.2%), unilateral disease and bilateral irradiation and 81 (27.3%), bilateral disease and bilateral irradiation. Thirty-four (9.7%) and 217 (62.0%) patients received neoadjuvant and/or concomitant chemotherapy, respectively. Median follow-up was 37 months. Three-year local, regional, locoregional failure rates and CUP-specific survival were 5.6%, 11.7%, 15.0% and 84.7%, respectively. In patients with unilateral disease, the 3-year cumulative incidence of regional/local relapse was 7.7%/4.3% after bilateral irradiation versus 16.9%/11.1% after unilateral irradiation (hazard ratio = 0.56/0.61, p = 0.17/0.32). The cumulative incidence of CUP-specific deaths was 9.2% after bilateral irradiation and 15.5% after unilateral irradiation (p = 0.92). In multivariate analysis, mucosal irradiation was associated with better local control, whereas no neck dissection, ≥N2b and interruption of RT for more than 4 days were associated with poorer regional control. Toxicity was higher after bilateral irradiation (p 0.05). No positron-emission tomography-computed tomography, largest node diameter, ≥N2b, neoadjuvant chemotherapy and interruption of RT were associated with poorer cause-specific survival.Bilateral nodal irradiation yielded non-significant better nodal and mucosal control rates but was associated with higher rates of severe toxicity.
- Published
- 2019
44. Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study
- Author
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Ezra E W Cohen, Denis Soulières, Christophe Le Tourneau, José Dinis, Lisa Licitra, Myung-Ju Ahn, Ainara Soria, Jean-Pascal Machiels, Nicolas Mach, Ranee Mehra, Barbara Burtness, Pingye Zhang, Jonathan Cheng, Ramona F Swaby, Kevin J Harrington, Mirelis Acosta-Rivera, Douglas R. Adkins, Morteza Aghmesheh, Mario Airoldi, Eduardas Aleknavicius, Yousuf Al-Farhat, Alain P. Algazi, Salah Almokadem, Anna Alyasova, Jessica R. Bauman, Marco Benasso, Alfonso Berrocal, Victoria Bray, Barbara Ann Burtness, Francesco Caponigro, Ana Castro, Terrence P. Cescon, Kelvin Chan, Arvind Chaudhry, Bruno Chauffert, Ezra Cohen, Tibor Csoszi, J.P. De Boer, Jean-Pierre Delord, Andreas Dietz, Jose Dinis, Charlotte Dupuis, Laurence Digue, Jozsef Erfan, Yolanda Escobar Alvarez, Mererid Evans, Mary Jo Fidler, Martin David Forster, Signe Friesland, Apar K. Ganti, Lionnel Geoffrois, Cliona Grant, Viktor Gruenwald, Kevin Harrington, Thomas Hoffmann, Geza Horvai, Arturas Inciura, Raymond Jang, Petra Jankowska, Antonio Jimeno, Mano Joseph, Alejandro Juarez Ramiro, Boguslawa Karaszewska, Andrzej Kawecki, Ulrich Keilholz, Ulrich Keller, Sung-Bae Kim, Judit Kocsis, Nuria Kotecki, Mark F. Kozloff, Julio Lambea, Laszlo Landherr, Yuri Lantsukhay, Sergey Alexandrovich Lazarev, Lip Way Lee, Igor Dmitrievich Lifirenko, Danko Martincic, Oleg Vladmirovhich Matorin, Margaret McGrath, Krzysztof Misiukiewicz, John C. Morris, Fagim Fanisovich Mufazalov, Jiaxin Niu, Devraj Pamoorthy Srinivasan, Pedro Perez Segura, Daniel Rauch, Maria Leonor Ribeiro, Cristina Rodriguez, Frederic Rolland, Antonio Russo, Agnes Ruzsa, Frederico Sanches, Sang-Won Shin, Mikhail Shtiveland, Denis Soulieres, Pol Specenier, Eva Szekanecz, Judit Szota, Carla M.L. van Herpen, Hector A. Velez-Cortes, William V. Walsh, Stefan Wilop, Ralph Winterhalder, Marek Wojtukiewicz, Deborah Wong, Dan Zandberg, KEYNOTE-040 investigators, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - (SLuc) Centre du cancer, and UCL - (SLuc) Unité d'oncologie médicale
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Male ,Oncology ,medicine.medical_specialty ,Combination therapy ,Population ,Cetuximab ,Phases of clinical research ,Docetaxel ,Kaplan-Meier Estimate ,Pembrolizumab ,030204 cardiovascular system & hematology ,Antibodies, Monoclonal, Humanized ,Drug Administration Schedule ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Clinical endpoint ,Humans ,030212 general & internal medicine ,education ,Aged ,ddc:616 ,education.field_of_study ,Squamous Cell Carcinoma of Head and Neck ,business.industry ,Hazard ratio ,General Medicine ,Middle Aged ,Methotrexate ,Head and Neck Neoplasms ,Disease Progression ,Female ,Human medicine ,Neoplasm Recurrence, Local ,business ,medicine.drug - Abstract
Summary Background There are few effective treatment options for patients with recurrent or metastatic head-and-neck squamous cell carcinoma. Pembrolizumab showed antitumour activity and manageable toxicity in early-phase trials. We aimed to compare the efficacy and safety of pembrolizumab versus standard-of-care therapy for the treatment of head-and-neck squamous cell carcinoma. Methods We did a randomised, open-label, phase 3 study at 97 medical centres in 20 countries. Patients with head-and-neck squamous cell carcinoma that progressed during or after platinum-containing treatment for recurrent or metastatic disease (or both), or whose disease recurred or progressed within 3–6 months of previous multimodal therapy containing platinum for locally advanced disease, were randomly assigned (1:1) in blocks of four per stratum with an interactive voice-response and integrated web-response system to receive pembrolizumab 200 mg every 3 weeks intravenously or investigator's choice of standard doses of methotrexate, docetaxel, or cetuximab intravenously (standard-of-care group). The primary endpoint was overall survival in the intention-to-treat population. Safety was analysed in the as-treated population. This trial is registered with ClinicalTrials.gov, number NCT02252042, and is no longer enrolling patients. Findings Between Dec 24, 2014, and May 13, 2016, 247 patients were randomly allocated to pembrolizumab and 248 were randomly allocated to standard of care. As of May 15, 2017, 181 (73%) of 247 patients in the pembrolizumab group and 207 (83%) of 248 patients in the standard-of-care group had died. Median overall survival in the intention-to-treat population was 8·4 months (95% CI 6·4–9·4) with pembrolizumab and 6·9 months (5·9–8·0) with standard of care (hazard ratio 0·80, 0·65–0·98; nominal p=0·0161). Fewer patients treated with pembrolizumab than with standard of care had grade 3 or worse treatment-related adverse events (33 [13%] of 246 vs 85 [36%] of 234). The most common treatment-related adverse event was hypothyroidism with pembrolizumab (in 33 [13%] patients) and fatigue with standard of care (in 43 [18%]). Treatment-related death occurred in four patients treated with pembrolizumab (unspecified cause, large intestine perforation, malignant neoplasm progression, and Stevens-Johnson syndrome) and two patients treated with standard of care (malignant neoplasm progression and pneumonia). Interpretation The clinically meaningful prolongation of overall survival and favourable safety profile of pembrolizumab in patients with recurrent or metastatic head and neck squamous cell carcinoma support the further evaluation of pembrolizumab as a monotherapy and as part of combination therapy in earlier stages of disease. Funding Merck Sharp & Dohme, a subsidiary of Merck & Co.
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- 2019
45. Afatinib as second-line treatment in patients with recurrent/metastatic squamous cell carcinoma of the head and neck: Subgroup analyses of treatment adherence, safety and mode of afatinib administration in the LUX-Head and Neck 1 trial
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Eleftherios Zografos, Lisa Licitra, Paul Clement, Luciano de Souza Viana, Yuan Geng, Joël Guigay, Sylvie Zanetta-Devauges, Didier Cupissol, Jérôme Fayette, Robert I. Haddad, Thomas Gauler, Gabriela Kornek, Ulisses Ribaldo Nicolau, Lionnel Geoffrois, Bohuslav Melichar, Daniel Rauch, Ezra E.W. Cohen, Ulrich Keilholz, Makoto Tahara, Jean-Pascal Machiels, Jan B. Vermorken, and Frederic Rolland
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Male ,Cancer Research ,medicine.medical_specialty ,Nausea ,Afatinib ,Medizin ,Gastroenterology ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Medicine ,Humans ,030223 otorhinolaryngology ,Adverse effect ,610 Medicine & health ,Stomatitis ,Feeding tube ,Aged ,business.industry ,Squamous Cell Carcinoma of Head and Neck ,Hazard ratio ,medicine.disease ,Head and neck squamous-cell carcinoma ,Rash ,ErbB Receptors ,Treatment Adherence and Compliance ,Methotrexate ,Treatment Outcome ,Oncology ,Head and Neck Neoplasms ,030220 oncology & carcinogenesis ,Quinazolines ,Female ,Human medicine ,Oral Surgery ,medicine.symptom ,Neoplasm Recurrence, Local ,business ,medicine.drug - Abstract
Objectives: Patients with head and neck squamous cell carcinoma (HNSCC) can experience severe symptom burden and/or difficulty swallowing, leading to problems with treatment adherence/administration. In LUXHead and Neck 1 (LH & N1; NCT01345682), second-line afatinib improved progression-free survival (PFS) versus methotrexate in patients with recurrent/metastatic HNSCC. We report adherence and safety across pre-specified and additional subgroups potentially linked to afatinib PFS benefit in LH&N1 (p16 status, smoking history), and afatinib adherence, safety and efficacy by administration (oral versus feeding tube; post-hoc analysis). Methods: Patients were randomized (2:1) to afatinib (40 mg/day) or intravenous methotrexate (40 mg/m(2)/ week). Results: Among 320 afatinib-treated and 160 methotrexate-treated patients, 83-92% and 76-92% (of patients with data available) across all subgroups took >= 80% of treatment. Across p16 status and smoking history subgroups, the most common treatment-related adverse events (AEs) were diarrhea (70-91%), rash/acne (72-84%), stomatitis (34-73%) with afatinib; and included stomatitis (39-100%), fatigue (22-50%), nausea (19-36%) with methotrexate. Dose reduction decreased AE incidence/severity. Baseline characteristics were generally similar between oral/feeding tube (n = 276/n = 46) groups. 89%/89% (of patients with data available) took >= 80% of assigned afatinib. Median PFS was 2.6 versus 2.7 months (hazard ratio: 0.997; 95% confidence interval: 0.72-1.38). The most common afatinib-related AEs were: rash/acne (74% versus 74%), diarrhea (73% versus 65%), stomatitis (40% versus 30%). Conclusion: Subgroup analyses of LH&N1 demonstrate that afatinib has predictable and manageable safety across patient subgroups, with high treatment adherence, and is effective via oral and feeding tube administration.
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- 2019
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46. Adaptation of chemotherapy to the decline tumor markers in patients with poor prognosis nonseminomatous germ cell tumors:Real-world French experience
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Marion Rolland, Guilhem Roubaud, Sara Faouzi, Damien Pouessel, Brigitte Laguerre, Magalie Pascale Tardy, Marine Gross-Goupil, Clement Dumont, Ludovic Doucet, Hakim Mahammedi, Christine Chevreau, Aude Flechon, Lionnel Geoffrois, Mathilde Guerin, Leonor Chaltiel, Diego Tosi, Karim Fizazi, and Stéphane Oudard
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Oncology ,Cancer Research ,Chemotherapy ,medicine.medical_specialty ,Poor prognosis ,business.industry ,medicine.medical_treatment ,medicine.disease ,Internal medicine ,medicine ,In patient ,Germ cell tumors ,Adaptation ,business ,Tumor marker - Abstract
385 Background: Personalized chemotherapy based on tumor marker decline is the new standard in poor prognosis germ-cell tumor in Europe since 2014 (GETUG 13, Lancet, Fizazi et al). The purpose of this study was to analyze the reproducibility of the princeps study in patients not selected in clinical routine between 2014 and 2018. Methods: Patients (pts) were eligible if they had at least one criteria of IGCCCG classification for poor prognosis group. They had to be treated according the study terms of GETUG 13 study and did not received prior treatment. They had to received 1 BEP (Bleomycin, Etoposide, Cisplatin). Tumor markers (HCG and AFP) were dosed between day 18 and 21. Then, they received 3 additional BEP if they had favorable tumor marker decline or intensive chemotherapy if they had unfavorable decline. Results: This retrospective study included 104 patients in 14 french centers treated between 2013 and 2018: 22,1 % (n = 23) in the favorable group (Fav), 77,9 % (n = 81) in the unfavorable group (Unfav). Thirty-two pts had PS ≥ 2. In Unfav, there were more pts with HCG > 50 000 UI/L (44,2 % vs 13 %, p = 0,0067), neutrophil-to-lymphocyt ratio was also higher (median 6,4 vs 4,5, p = 0,0199). At cycle 1, all pts received BEP in Fav and 87,5 % (n = 70) in Unfav. After chemotherapy and surgery, 65,2 % in Fav and 41,3 % in Unfav obtained complete response. At 30 months (median follow-up), Fav-OS was 80,5 % (IC95% 55,8 – 92,2) and Unfav-OS was 64,4 % (IC95% 52 – 74,4). At 30 months, rates were 69,6 % (IC95% 46,6 -84,2) and 63.5 % (IC95% 51,9 – 73) respectively. In GETUG 13 study, 3-years OS was 84 % in Fav and 73 % on Unfav; 3-years PFS was 70 % and 59 % respectively. Seven pts died because of toxicity in Unfav (No one in Fav). Neuropathy, anemia and thrombopenia were more frequent in Unfav. Salvage high-dose chemotherapy with stem-cell transplant was required in 4 (66,7 %) pts in Fav and 8 (36,4 %) pts in Unfav. Conclusions: This study showed a reproducibility of the princeps study in terms of PFS and OS. Toxicity seemed more important in real world. For the congress, results will be reported with 50 additional pts.
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- 2021
47. Association of statins and nivolumab activity in patients with metastatic renal cell carcinoma (mRCC): Results from the phase II nivoren—GETUG AFU 26 trial
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Lionnel Geoffrois, Florence Tantot, Brigitte Laguerre, Antoine Thiery-Vuillemin, Sylvie Negrier, Bernard Escudier, Gwenaelle Gravis, Florence Joly, Christine Chevreau, Marine Gross Goupil, Sylvain Ladoire, Stéphane Oudard, Cécile Dalban, Laurence Albiges, Ronan Flippot, Emeline Colomba, Philippe Barthélémy, and Frederic Rolland
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Cancer Research ,Immune system ,Oncology ,Renal cell carcinoma ,business.industry ,Oncogenic signaling ,medicine ,Cancer research ,In patient ,Tumor growth ,Nivolumab ,medicine.disease ,business - Abstract
359 Background: Statins are HMG-CoA inhibitors that regulate several mechanisms involved in tumor growth, including mitochondrial metabolism, activation of oncogenic signaling pathways, and immune modulation. Population-based studies showed that statin intake may be negatively associated with RCC onset. The impact of statins on response to immunotherapy in mRCC is unknown. Herein we study the association between statin administration and outcomes in patients with mRCC treated with nivolumab in the NIVOREN-GETUG AFU 26 phase II trial (NCT03013335). Methods: Patients with mRCC who failed previous VEGFR inhibitors were included. We assessed nivolumab activity, including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) according to statin intake at baseline. Toxicity was assessed using CTCAE v4.0. Results: Overall,133 patients were treated with statins at baseline among 702 evaluable for concomitant therapies (19%). Among them, median age was 68 (49-90), 84% were male, 85% had a performance status ≥ 80%, 42% were overweight and 20% obese. Patients treated with statins had mostly good (23%) or intermediate (58%) IMDC risk, 64% had grade 3 or 4 tumors, and nivolumab was given in a third line setting or more in 55%. Median follow-up was 23.9 months (95%CI 23.0-24.5) in the overall cohort. The ORR was 26% in patients treated with statins, PFS 5.0 months (CI95% 3.0 – 5.5), OS 27.9 months (CI95% 19.4-30.3). Outcomes of patients with or without statins did not differ significantly. Similar rates of grade 3-5 TRAE were reported in patients with (20%) or without (18%) statin intake. Conclusions: This is the first study to evaluate statin intake and outcomes with nivolumab in patients with mRCC. Despite numerically higher ORR, statins were not significantly associated with improved outcomes. These data require other analyzes considering other factors such as BMI and other comorbidities. Further studies may help better understand the interplay between immunity and metabolic reprogramming in RCC.
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- 2021
48. Safety and efficacy of nivolumab in older patients (pts) with renal cell carcinoma: Results of a sub-group analysis of the GETUG-AFU 26 NIVOREN multicenter phase II study
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Philippe Barthélémy, Loic Mourey, Laurence Albiges, Sylvie Negrier, Gwenaelle Gravis, Florence Joly, Marine Gross-Goupil, Delphine Borchiellini, Christine Chevreau, Brigitte Laguerre, Florence Tantot, Cécile Dalban, Lionnel Geoffrois, Frederic Rolland, Antoine Thiery-Vuillemin, Bernard Escudier, Sylvain Ladoire, and Constance Thibault
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Phases of clinical research ,medicine.disease ,Older patients ,Renal cell carcinoma ,Internal medicine ,Medicine ,Nivolumab ,business ,Prospective cohort study - Abstract
331 Background: NIVOREN GETUG AFU 26 study, is a french multicenter prospective study to evaluate safety and efficacy of Nivolumab (N) in a broad “real world setting” in mRCC after failure of 1 or 2 tyrosine kinase inhibitors. Methods: Between February 2016 and July 2017, 729 pts were enrolled across 27 institutions. Primary objective of the trial was safety assessed by grade ≥ 3 treatment related adverse event (TRAE). We report here results of older patients above 70 years old ([70;75[; [75;80[; ≥ 80) compared with their younger counterparts. Results: Overall, 720 patients were treated (median age 64 (22;90)). Among them 205 pts were ≥ 70 (28.5%) divided as follow: [70-75[:107 (14.9%) / [75-80[: 68 (9,4%) / ≥ 80: 30 (4,2%). Patients’ characteristics (Table) were similar in younger and older patients except for IMDC risk groups (IMDC) classification with less poor prognostic in pts ≥ 75 and fewer brain metastasis in pts ≥ 70. Treatment duration was similar across age groups despite a rate of discontinuation for TRAE increasing with age. Regarding efficacy, there was a non-significant trend toward improved response rate and progression free survival and lower specific survival with increasing age. Conclusions: In this large “real world” setting study a significant number of old pts were included. Prognostic profile appears better in older pts included. There is no signal for an excess of toxicity in this population and efficacy is comparable to younger patients. Age alone should not prevent prescribing N in mRCC. Clinical trial information: NCT03013335 . [Table: see text]
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- 2021
49. Long-term update of the 24954 EORTC phase III trial on larynx preservation
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D. De Raucourt, Catherine Fortpied, Livia Giurgea, Lisa Licitra, Charles R. Leemans, Jessica Menis, L. Barzan, Vincent Grégoire, Jan B. Vermorken, Frederic Rolland, M. Tesselaar, Lionnel Geoffrois, B. Henriques De Figueiredo, J.L. Lefebvre, P. Hupperets, RS: FHML non-thematic output, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Interne Geneeskunde, MUMC+: MA Medische Oncologie (9), EORTC Head Neck Canc Grp, EORTC Radiation Oncology Cooperati, Otolaryngology / Head & Neck Surgery, and CCA - Evaluation of Cancer Care
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Male ,Larynx ,Cancer Research ,medicine.medical_treatment ,0302 clinical medicine ,Antineoplastic Combined Chemotherapy Protocols ,030223 otorhinolaryngology ,Dose Fractionation ,Radiation ,Hypopharyngeal cancer ,Chemoradiotherapy ,Middle Aged ,Laryngeal Neoplasm ,Laryngectomy ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Carcinoma, Squamous Cell ,Disease Progression ,Female ,Fluorouracil ,Late toxicity ,Adult ,medicine.medical_specialty ,Young Adult ,03 medical and health sciences ,Larynx preservation ,medicine ,Humans ,Laryngeal Neoplasms ,Radiochemotherapy ,Survival analysis ,Aged ,Hypopharyngeal Neoplasms ,business.industry ,Carcinoma ,Dose fractionation ,medicine.disease ,Survival Analysis ,Surgery ,Radiation therapy ,Cisplatin ,Dose Fractionation, Radiation ,Organ Sparing Treatments ,Squamous Cell ,Human medicine ,business - Abstract
The long-term results of the EORTC 24954 trial comparing sequential versus alternating chemotherapy and radiotherapy (RT) for patients with locally advanced laryngeal and hypopharyngeal cancer are reported. From 1996 to 2004, 450 patients were randomly assigned (1-1) to a sequential arm (SA = induction cisplatin-5fluorouracil followed by a 70Gy-RT for the responders or a total laryngectomy and post-operative RT for the non-responders) and an alternating arm (AA = cisplatin-5fluorouracil alternated with three 2-week courses of 20 Gy-RT for a total dose of 60 Gy). Median follow-up was 10.2 years. Ten-year survival with functional larynx (primary end-point) and overall survival were similar in both arms (18.7% and 33.6% in SA versus 18.3% and 31.6% in AA). Late toxicity was also similar; however, a trend for higher larynx preservation and better laryngeal function was observed in AA. (C) 2016 Elsevier Ltd. All rights reserved.
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- 2016
50. LBA38 Pembrolizumab versus cetuximab, concomitant with radiotherapy (RT) in locally advanced head and neck squamous cell carcinoma (LA-HNSCC): Results of the GORTEC 2015-01 'PembroRad' randomized trial
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F. Drouet, A. Pechery, M. Rives, Alexandre Coutte, M. Wanneveich, Julian Biau, Joël Guigay, J.B. Prevost, X. Liem, Yungan Tao, Jean Bourhis, Marc Alfonsi, Lionnel Geoffrois, Jean-Marc Tourani, Cedrik Lafond, Elodie Vauleon, Anne Auperin, Christian Sire, X. Sun, and Laurent Martin
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Oncology ,medicine.medical_specialty ,Cetuximab ,business.industry ,medicine.medical_treatment ,Locally advanced ,Hematology ,Pembrolizumab ,medicine.disease ,Head and neck squamous-cell carcinoma ,law.invention ,Radiation therapy ,Randomized controlled trial ,law ,Concomitant ,Internal medicine ,medicine ,business ,medicine.drug - Published
- 2020
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