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Your search keyword '"Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO)"' showing total 5 results
Start Over Author "Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO)" Journal european journal of cancer (oxford, england : 1990)
5 results on '"Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO)"'

1. A phase II randomised study of preoperative trastuzumab alone or combined with everolimus in patients with early HER2-positive breast cancer and predictive biomarkers (RADHER trial)

Author

Barbara Pistilli, Marta Jimenez, Thomas Bachelot, Fabrice Andre, Keyvan Rezai, Julia Salleron, Laurence Vanlemmens, Jean-Louis Merlin, Mario Campone, Valérie Seegers, Qing Wang, Maëva Lion, Agnès Leroux, Gilles Paintaud, Isabelle Treilleux, Delphine Loussouarn, Véronique Diéras, Monica Arnedos, Maria Rios, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Département cancer environnement (Centre Léon Bérard - Lyon), Centre Léon Bérard [Lyon], Institut Gustave Roussy (IGR), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Institut Curie [Paris], Génétique, immunothérapie, chimie et cancer (GICC), UMR 7292 CNRS [2012-2017] (GICC UMR 7292 CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Hôpital René HUGUENIN (Saint-Cloud), Centre de Recherche en Automatique de Nancy (CRAN), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), Université de Tours-Centre National de la Recherche Scientifique (CNRS), 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), Université de Lille-UNICANCER, Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT), and Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Oncology, Cancer Research, medicine.medical_specialty, Combination therapy, [SPI.AUTO]Engineering Sciences [physics]/Automatic, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Trastuzumab, Internal medicine, Mucositis, Medicine, PI3K/AKT/mTOR, Everolimus, skin and connective tissue diseases, PI3K/AKT/mTOR pathway, 030304 developmental biology, 0303 health sciences, business.industry, Biomarker, HER2+ breast cancer, medicine.disease, Rash, 3. Good health, 030220 oncology & carcinogenesis, Biomarker (medicine), medicine.symptom, business, medicine.drug
Abstract

Introduction Resistance to trastuzumab in breast cancer is an ongoing challenge. Clinical and biological effects of co-targeting HER2 and mammalian target of rapamycin (mTOR) in patients with HER2-positive early operable breast cancer via the addition of everolimus to preoperative trastuzumab were evaluated in a phase II randomised study. Methods Patients were randomised 1:1 to receive trastuzumab (4 mg/kg initial dose then 2 mg/kg weekly for 5 weeks) alone or combined with everolimus (10 mg/day for 6 weeks) and then underwent surgery. Tumours were assessed by clinical examination and echography at the baseline and on treatment. The primary end-point was the clinical response rate at 6 weeks. Pathological response and safety were also evaluated. Baseline and surgery tumour samples were assessed by immunohistochemistry and multiplex immunoanalysis for predictive downstream effectors of the PI3K/AKT/mTOR and MAP kinase (MAPK) pathways. Results Eighty-two patients were enrolled, 41 per arm. The clinical response rates were 34.1% and 43.9% with trastuzumab alone and combined with everolimus, respectively. Pathological response rates were 43.6% and 47.5%, respectively. Addition of everolimus increased toxicity, notably mucositis (82.5% versus 5.0%) and rash (57.5% versus 10.0%), but grade III/IV events were rare. No correlation between response to treatments and baseline candidate biomarkers was identified, except for PIK3CA mutations which were found to predict trastuzumab resistance. Significant changes were seen in several MAPK pathway effectors after combination therapy. Conclusions The addition of everolimus did not improve the efficacy, but induced MAPK signalling. Combination therapy to overcome pathway cross-talk should be considered to maximise the effectiveness of trastuzumab in this setting. ClinicalTrial.gov Identifier NCT00674414.

Published
2021

2. Axitinib in first-line for patients with metastatic papillary renal cell carcinoma: Results of the multicentre, open-label, single-arm, phase II AXIPAP trial

Author

Lionel Geoffrois, David Pérol, Celine Ferlay, Ellen Blanc, Frederic Rolland, Alain Ravaud, Laurence Albiges, Gwenaelle Gravis, Marine Gross-Goupil, Bernard Escudier, Christine Chevreau, Slimane Dermeche, Aude Flechon, Nathalie Rioux-Leclercq, Sylvie Negrier, Helen Boyle, Centre Léon Bérard [Lyon], Service de Pathologie [Rennes] = Pathology [Rennes], CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Département d'oncologie médicale, Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Département d'Oncologie Médicale, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Institut Claudius Regaud, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Délégation à la Recherche Clinique et à l'Innovation [Lyon] (DRCI), Centre Léon Bérard [Lyon]-UNICANCER - Centre Léon Bérard Lyon (Rhône), Département d'Oncologie [CHU Bordeaux] (Cancérologie/Oncologie/Digestive), Hôpital Haut-Lévêque - CHU de Bordeaux (Centre médico chirurgical Magellan)-Hôpital Saint-André [CHU de Bordeaux], Department of Oncology, CHU Pointe-à-Pitre/Abymes [Guadeloupe], Service d'Oncologie Médicale [Centre hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Oncologie génito-urinaire, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Institut Gustave Roussy (IGR), Hematopoïèse et Cellules Souches (U362), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pfizer, Centre Léon Bérard., Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), UNICANCER - Centre Léon Bérard Lyon (Rhône)-Centre de Lutte Contre le Cancer de Lyon et Rhône-Alpes, and GH Sud Haut-Lévêque [CHU Hôpitaux de Bordeaux] (Centre médico chirurgical Magellan)-Hôpital Saint-André [CHU de Bordeaux]

Subjects
0301 basic medicine, Adult, Male, Cancer Research, medicine.medical_specialty, Axitinib, [SDV]Life Sciences [q-bio], Urology, Phases of clinical research, Administration, Oral, Papillary renal cell carcinoma, Drug Administration Schedule, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, medicine, Humans, Progression-free survival, Adverse effect, Tyrosine kinase, Carcinoma, Renal Cell, Protein Kinase Inhibitors, Advanced renal cancer, Aged, Aged, 80 and over, Papillary renal cell carcinomas, business.industry, Remission Induction, Middle Aged, Confidence interval, Kidney Neoplasms, Progression-Free Survival, 3. Good health, Vascular endothelial growth factor, Clinical trial, 030104 developmental biology, Receptors, Vascular Endothelial Growth Factor, Oncology, chemistry, 030220 oncology & carcinogenesis, Hypertension, Female, business, medicine.drug, VEGF inhibitor, Follow-Up Studies
Abstract

International audience; Introduction: Papillary renal cell carcinoma (PRCC) represents 10%e15% of renal carcinomas. No standard treatments exist for metastatic PRCC (mPRCC) patients. Axitinib is indicated as second-line treatment in metastatic clear cell renal carcinoma, and we aim to assess the efficacy of this vascular endothelial growth factor receptor inhibitor in front line for mPRCC. Methods: This French multicentre phase II study AXIPAP enrolled untreated mPRCC patients, with measurable disease, Eastern Cooperative Oncology Group performance status 1 and Vascular endothelial growth factor; VEGF inhibitor; Targeted therapy adequate organ functions. PRCC had to be confirmed by histology expert central review. Axi-tinib was administered orally 5 mg twice daily. Primary end-point was progression-free rate at 24 weeks (24w-PFR) by central review. Results: Fifty-six patients were screened, and 44 included (13 type 1, 30 type 2 and 1 non-specified). The median follow-up was 32.0 (13.1e39.9) months. The 24w-PFR was 45.2% (95% confidence interval [CI], 32.6% to þN), the objective response rate was 28.6% (95% CI, 15.7%e44.6%) (type 1: 7.7%; type 2: 35.7%). The overall median progression free survival was 6.6 months (95% CI, 5.5e9.2), 6.7 months (95% CI, 5.5e9.2) and 6.2 months (95% CI, 5.4 e9.2) for type 1 and 2, respectively. Median overall survival was 18.9 months (95% CI, 12.8enot reached). Adverse events were as expected; grade 3e4 treatment-related adverse events were rare except hypertension (27%). Conclusions: Axitinib demonstrated encouraging efficacy in mPRCC patients, especially in type 2 PRCC. Toxicity was manageable. Axitinib appears as an interesting option for first-line treatment and to be worth further investigation in combination with immunotherapy in these patients. Expert pathology review should be recommended in this setting. Clinical trial registration: ClinicalTrials.gov, NCT02489695.

Published
2019

3. Osteoporosis treatment and 10 years' oestrogen receptor+ breast cancer outcome in postmenopausal women treated with aromatase inhibitors

Author

Mario Campone, Olivier Capitain, Patrick Soulié, Béatrice Bouvard, J Chatelais, N. Mesgouez-Nebout, Emmanuel Hoppé, Martine Mege, Patrick Saulnier, Eric Jadaud, Sophie Abadie-Lacourtoisie, Erick Legrand, Groupe d'Études Remodelage Osseux et bioMatériaux (GEROM), Université d'Angers (UA), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Micro et Nanomédecines Translationnelles (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Centre de Lutte Contre le Cancer Nantes Atlantique 'René Gauducheau' (CLCC)

Subjects
0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, medicine.drug_class, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Osteoporosis, Breast Neoplasms, vitamin D deficiency, 03 medical and health sciences, Fractures, Bone, 0302 clinical medicine, Breast cancer, breast cancer, Bone Density, Internal medicine, Outcome Assessment, Health Care, Vitamin D and neurology, Medicine, Humans, Longitudinal Studies, Prospective Studies, Vitamin D, Prospective cohort study, bisphosphonates, Osteoporosis, Postmenopausal, Aged, Aromatase inhibitor, Bone Density Conservation Agents, Diphosphonates, business.industry, Aromatase Inhibitors, Cancer, Vitamins, Bisphosphonate, Middle Aged, medicine.disease, osteoporosis, 3. Good health, Postmenopause, 030104 developmental biology, Receptors, Estrogen, 030220 oncology & carcinogenesis, Female, business
Abstract

International audience; BACKGROUND: Risk factors for breast cancer relapse are well-known, such as large tumour size or lymph node involvement. The aim of our study was to analyse the influence of bone mineral density, fractures and bisphosphonate or vitamin D prescription on 10 years' breast cancer outcome.PATIENTS AND METHODS: This is a longitudinal and prospective cohort of 450 postmenopausal women with local oestrogen receptor (ER)+ breast cancer. For every patient, we analysed tumour characteristics, bone status at the beginning of aromatase inhibitor treatment and 10 years' cancer outcome with Cox model.RESULTS: Mean follow-up was 10.3±3.0 years. Seventy nine women died, and 75 had a relapse; 30.7% had a history of fracture, 16.9% had a T-score≤-2.5and 11.3% had vitamin D deficiency. Bisphosphonates were prescribed to 35.3% women for osteoporosis for a mean duration of 5±1.7 years. Tumour size (hazard ratio [HR]=1.32, P≤0.01) and the number of lymph nodes involved (HR=1.07, P=0.03) were significantly associated with relapse. Bisphosphonate treatment was significantly associated with a decreased risk of relapse (HR=0.51, P=0.03). Age at cancer diagnosis (HR=1.07, P≤0.01) and vitamin D deficiency (HR=1.85, P=0.04) were significantly associated with an increased risk of death, whereas bisphosphonate treatment was associated with a decreased risk of death (HR=0.46, P=0.01).CONCLUSION: Osteoporosis treatment, including vitamin D and bisphosphonates, is associated with a 50% reduction of relapse and death in women treated with aromatase inhibitors for ER+ breast cancer.

Published
2018

4. Time trends of overall survival among metastatic breast cancer patients in the real-life ESME cohort

Author

Laurence Vanlemmens, Marc Debled, Christian Cailliot, Elisa Gobbini, Thomas Bachelot, Monia Ezzalfani, Christelle Jouannaud, Suzette Delaloge, Magali Lacroix-Triki, Anne Patsouris, Thierry Petit, Simone Mathoulin-Pélissier, Veronique Lorgis, William Jacot, Marie Ange Mouret-Reynier, Mathieu Robain, C. Lefeuvre-Plesse, Florence Dalenc, Audrey Lardy Cleaud, Etienne Brain, Christelle Levy, David Pérol, C. Courtinard, Véronique Diéras, Marianne Leheurteur, Lionel Uwer, Anthony Gonçalves, Jean Marc Ferrero, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Institut Curie [Paris]-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute Curie, Centre Léon Bérard [Lyon], Institut Curie [Saint-Cloud], Service d'Oncologie Médicale, CRLCC Haute Normandie-Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), CRLC Val d'Aurelle-Paul Lamarque, CRLCC Val d'Aurelle - Paul Lamarque, 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), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), École nationale supérieure d'architecture de Toulouse (ENSA Toulouse), Centre de Recherches en Cancérologie de Toulouse (CRCT), 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)-Centre National de la Recherche Scientifique (CNRS), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Service d'Oncologie médicale [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Department of Medical Oncology, CRLCC Eugène Marquis (CRLCC), Centre d'Investigation Clinique - Epidemiologie Clinique / Essais Cliniques Bordeaux, Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Jean Godinot, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Département de biologie et pathologie médicales [Gustave Roussy], Cancer et génôme: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Haute Normandie-CRLCC Henri Becquerel, CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie Moléculaire et Stratégies Théranostiques - Clermont Auvergne (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Institut de cancérologie de l'Ouest - Paul Papin (ICO - Paul Papin), Service d'oncologie Médicale, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Center Oscar Lambret, CRLCC Oscar Lambret, Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), 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 Curie - Saint Cloud (ICSC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Lille-UNICANCER

Subjects
Adult, Cancer Research, medicine.medical_specialty, Multivariate analysis, Time Factors, Receptor, ErbB-2, [SDV.CAN]Life Sciences [q-bio]/Cancer, Breast Neoplasms, Triple Negative Breast Neoplasms, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Cancer Survivors, Risk Factors, HER2, Internal medicine, polycyclic compounds, Overall survival, Biomarkers, Tumor, Medicine, Humans, 030212 general & internal medicine, Neoplasm Metastasis, skin and connective tissue diseases, Aged, Retrospective Studies, Subtypes, Aged, 80 and over, business.industry, Time trends, Hazard ratio, Middle Aged, Metastatic breast cancer, medicine.disease, Confidence interval, 3. Good health, Treatment Outcome, Oncology, Receptors, Estrogen, 030220 oncology & carcinogenesis, Cohort, Observational study, Female, France, business, Receptors, Progesterone
Abstract

Real-life analysis of overall survival (OS) trends among metastatic breast cancer (MBC) patients may help define medical needs and evaluate the impact of public health investments. The present study aimed to evaluate the independent impact of the year of MBC diagnosis on OS in the Epidemio-Strategy-Medical-Economical (ESME)-MBC cohort.ESME-MBC (NCT03275311) is a French, national, multicentre, observational cohort including 16,702 consecutive newly diagnosed MBC patients (01 January 2008-31 December 2014). Of 16,680 eligible patients, 15,085 had full immunohistochemistry data, allowing classification as hormone receptor-positive and HER2-negative (HR+/HER2-, N = 9907), HER2-positive (HER2+, N = 2861) or triple-negative (HR-/HER2-, N = 2317) subcohorts. Multivariate analyses of OS were conducted among the full ESME cohort and subcohorts.Median OS of the whole cohort was 37.22 months (95% confidence interval [CI], 36.3-38.04). Year of diagnosis was an independent predictor of OS (hazard ratio 0.98 [95% CI, 0.97-1.00], P = .01) together with age, subtype, disease-free interval, visceral metastases and number of organs involved. Median OS of HR+/HER2-, HER2+ and HR-/HER2- subcohorts was, respectively, 42.12 (95% CI, 40.90-43.10), 44.91 (95% CI, 42.51-47.90) and 14.52 (95% CI, 13.70-15.24) months. Year of diagnosis was a strong independent predictor of OS in HER2+ subcohort (hazard ratio 0.91 [95% CI, 0.88-0.94], P .001), but not in HR+/HER2- nor HR-/HER2- subcohorts (hazard ratio 1.00 [95% CI, 0.98-1.01], P = .80 and 1.00 [95% CI, 0.97-1.02], P = .90, respectively).The OS of MBC patients has slightly improved over the past decade. However, this effect is confined to HER2+ cases, highlighting the need of new strategies in the other subtypes.

Published
2018

5. Efficacy and safety of regorafenib compared to placebo and to post-cross-over regorafenib in advanced non-adipocytic soft tissue sarcoma

Author

Desmedt, Christine, Salgado, Roberto, Fornili, Marco, Pruneri, Giancarlo, van den Eynden, Gert, Zoppoli, Gabriele, Rothé, Françoise, Buisseret, Laurence, Garaud, Soizic, Willard-Gallo, Karen, Brown, David, Bareche, Yacine, Rouas, Ghizlane, Galant, Christine, Loi, Sherene, Viale, Giuseppe, Di Leo, Angelo, Green, Andrew, Ellis, Ian, Rakha, Emad, Larsimont, Denis, Biganzoli, Elia, Sotiriou, Christos, Brodowicz, Thomas, Mir, Olivier, Wallet, Jennifer, Italiano, Antoine, Blay, Jean-Yves, Bertucci, François, Eisterer, Wolfgang, Chevreau, Christine, Piperno-Neumann, Sophie, Bompas, Emmanuelle, Ryckewaert, Thomas, Liegl-Antzwager, Bernadette, Thery, Julien, Penel, Nicolas, Le Cesne, Axel, Le Deley, Marie-Cécile, Breast Cancer Translational Research Laboratory, Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), University of Pisa - Università di Pisa, European Institute of Oncology [Milan] (ESMO), IRCCS Ospedale Policlinico San Martino [Genoa, Italy], Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, Institut des Matériaux Jean Rouxel (IMN), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Ecole Polytechnique de l'Université de Nantes (EPUN), Université de Nantes (UN)-Université de Nantes (UN)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Cliniques Universitaires Saint-Luc [Bruxelles], Division of Pathology and Laboratory Medicine, Università degli Studi di Milano = University of Milan (UNIMI)-European Institute of Oncology [Milan] (ESMO), Translational Research Unit c/o Department of Oncology, Hospital of Prato, Istituto Toscano Tumori, Academic Centre on Rare Diseases (ACoRD), University College Dublin [Dublin] (UCD), Université médicale de Vienne, Autriche, Sarcome, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Bergonié [Bordeaux], UNICANCER, Centre Léon Bérard [Lyon], 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), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), 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), Département d'Oncologie Médicale [Institut Curie, Paris], Institut Curie [Paris], Département d'oncologie médicale [ICO, Saint Herblain], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, Département d'oncologie médicale, Ecole de Médecine [CHRU Lille], Università degli Studi di Milano [Milano] (UNIMI)-European Institute of Oncology [Milan] (ESMO), 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 d'Etudes Médiévales de Montpellier (CEMM), and Université Paul-Valéry - Montpellier 3 (UPVM)

Subjects
0301 basic medicine, Leiomyosarcoma, Oncology, Adult, Male, Cancer Research, medicine.medical_specialty, Pyridines, [SDV.CAN]Life Sciences [q-bio]/Cancer, Antineoplastic Agents, Kaplan-Meier Estimate, Placebo, Placebos, 03 medical and health sciences, chemistry.chemical_compound, Young Adult, 0302 clinical medicine, Double-Blind Method, Internal medicine, Regorafenib, medicine, Humans, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, Cross-Over Studies, Proportional hazards model, business.industry, Soft tissue sarcoma, Phenylurea Compounds, Hazard ratio, Sarcoma, Middle Aged, medicine.disease, Synovial sarcoma, Progression-Free Survival, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, Disease Progression, Female, business, Follow-Up Studies
Abstract

The placebo-controlled phase-2 REGOSARC trial demonstrated the efficacy of regorafenib in patients with leiomyosarcoma, synovial sarcoma and other non-adipocytic sarcoma but not in liposarcoma. Patients initially allocated to placebo were allowed to receive regorafenib after progression. We report here an updated analysis of the trial including evaluation of regorafenib activity after cross-over.From June 2013 to December 2014, 139 patients were enrolled in the non-adipocytic sarcoma cohorts. Median follow-up is now 32.4 months. Benefit of regorafenib versus placebo in terms of progression-free survival (PFS) and overall survival (OS) from randomisation was estimated by hazard ratio (HR) in Cox models. In the placebo arm, intra-patient benefit of regorafenib after cross-over was evaluated by the growth modulation index (GMI) (GMI was here, for each patient, PFS after cross-over regorafenib divided by PFS with placebo). Furthermore, the activity of delayed (after cross-over) versus early (at study entry) regorafenib was evaluated by comparing PFS after cross-over to regorafenib to PFS after randomisation in the regorafenib arm.PFS benefit of regorafenib as compared to placebo was confirmed with longer follow-up (HR = 0.50; 95% CI: 0.35-0.71; p .0001). OS was not statistically significant different (HR = 0.78; 0.54-1.12; p = .18). This finding may partially be explained by the fact that 55/68 patients who progressed on placebo (81%) received cross-over Regorafenib after progression: 59% of them had a GMI ≥ 1.3 (95% CI, 45-71%). Delayed start of regorafenib was associated with a statistically non-significant shorter PFS as compared to early treatment (HR = 1.21; 0.84-1.73; p = .30) without impact on OS.Observed PFS confirms that regorafenib warrants further clinical investigation in refractory non-adipocytic sarcomas.

Published
2018

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