A double-blind placebo-controlled randomized phase II trial assessing the activity and safety of regorafenib in non-adipocytic sarcoma patients previously treated with both chemotherapy and pazopanib

Autor: Sébastien Salas, Jennifer Wallet, Emilie Decoupigny, Thomas Brodowicz, Jean-Yves Blay, Christine Chevreau, Marie-Cécile Le Deley, Marie Vanseymortier, Olivier Mir, Axel Le Cesne, Loic Chaigneau, Lucie Laroche, François Bertucci, Esma Saada-Bouzid, Isabelle Ray-Coquard, Nicolas Penel, Sophie Taïeb, Corinne Delcambre, Emmanuelle Bompas, Antoine Italiano
Přispěvatelé: Université de Lille, Institut Gustave Roussy (IGR), Service de Biostatistiques [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Léon Bérard [Lyon], Département de médecine oncologique [Gustave Roussy], Université de Bordeaux (UB), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, 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), Medical Oncology Department [Nice], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), 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), Institut Claudius Regaud, Medizinische Universität Wien = Medical University of Vienna, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Direction de la recherche clinique et de l'innovation [CHU Amiens], CHU Amiens-Picardie, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay
Rok vydání: 2020
Předmět:
Male
0301 basic medicine
Cancer Research
Pyridines
medicine.medical_treatment
Soft Tissue Neoplasms
Kaplan-Meier Estimate
Gastroenterology
chemistry.chemical_compound
0302 clinical medicine
Antineoplastic Combined Chemotherapy Protocols
ComputingMilieux_MISCELLANEOUS
Sulfonamides
Cross-Over Studies
Soft tissue sarcoma
Hazard ratio
Anemia
Sarcoma
Middle Aged
Treatment Outcome
Oncology
030220 oncology & carcinogenesis
Disease Progression
Female
medicine.drug
Adult
Diarrhea
Chest Pain
medicine.medical_specialty
Indazoles
[SDV.CAN]Life Sciences [q-bio]/Cancer
Placebo
Pazopanib
03 medical and health sciences
Double-Blind Method
Regorafenib
Internal medicine
medicine
Humans
Adverse effect
Aged
Chemotherapy
business.industry
Phenylurea Compounds
Leukopenia
medicine.disease
Confidence interval
Pyrimidines
030104 developmental biology
chemistry
business
Zdroj: European Journal of Cancer
European Journal of Cancer, 2020, 126, pp.45-55. ⟨10.1016/j.ejca.2019.12.001⟩
ISSN: 0959-8049
DOI: 10.1016/j.ejca.2019.12.001
Popis: Background Metastatic soft tissue sarcomas (STSs) management remains an unmet medical need. We assessed the activity and safety of regorafenib in patients with metastatic non-adipocytic STS who were previously treated with both chemotherapy and pazopanib. Patients and methods This double-blind, placebo-controlled, multicenter comparative randomized phase II trial included patients with histologically proven advanced and inoperable STS. Patients receiving placebo were offered optional cross-over for centrally confirmed disease progression. Primary end-point was centrally reviewed Response Evaluation Criteria in Solid Tumours–based progression-free survival (PFS), analysed on the intent-to-treat data set. In total, 24 events were required for 90% power, hazard ratio (HR) = 0.33 (median PFS, 3.6 versus 1.2 months), and 1-sided α = 0.1 ( ClinicalTrials.gov , NCT01900743 ). Results From December 2015 to October 2017, 37 patients were randomized; 18 to regorafenib and 19 to placebo. Thirteen patients assigned to placebo switched to regorafenib after progression. Median follow-up was 27.2 months (95% confidence interval [CI]: 24.4–not reached). We observed a significant PFS benefit of regorafenib compared with placebo (adjusted HR = 0.33; 95% CI: 0.15–0.74; p = 0.0007 median PFS = 2.1 versus 1.1 months, respectively), and a large and nearly significant overall survival (OS) benefit despite the cross-over (adjusted HR = 0.49; 95% CI: 0.23–1.06; p = 0.007; median OS = 17.8 versus 8.2 months). Before cross-over, the most common grade III or higher adverse events were lymphopenia (5 versus 1, respectively), diarrhoea (4 versus 0), dyspnoea (3 versus 1), skin toxicity (3 versus 0), arterial hypertension (2 versus 0), and increased transaminases (2 versus 0). Conclusion The present study demonstrated a meaningful clinical anti-tumour activity with regorafenib in heavily pre-treated patients with non-adipocytic STS.
Databáze: OpenAIRE
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