Crizotinib in c-MET- or ROS1-positive NSCLC: results of the AcSé phase II trial
| العنوان: | Crizotinib in c-MET- or ROS1-positive NSCLC: results of the AcSé phase II trial |
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| المؤلفون: | Denis Moro-Sibilot, Renaud Sabatier, Alexis B. Cortot, Gérard Zalcman, S.D. Guibert, Fabrice Barlesi, Maurice Pérol, J. Otto, Ratislav Bahleda, Gilles Vassal, P.J. Souquet, Marta Jimenez, Nathalie Cozic, Gilbert Ferretti, Bertrand Mennecier, N. Hoog-Labouret, S. Bota, Marie Wislez, F. De Fraipont, Véronique Haddad, Julien Mazieres, C. Dubos, V. Verriele, Isabelle Monnet |
| المساهمون: | Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Département cancer environnement (Centre Léon Bérard - Lyon), Centre Léon Bérard [Lyon], Service de pneumologie [Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Service de pneumologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Intergroupe Francophone de Cancérologie Thoracique [Paris] (IFCT), Intergroupe Francophone de Cancérologie thoracique, Service d'oncologie multidisciplinaire innovations thérapeutiques [Hôpital Nord - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], 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), Service de Pneumologie [CHI Créteil], CHI Créteil, Service de pneumologie, oncologie thoracique et soins intensifs respiratoires [Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Laboratoire de Bactériologie CHU de Rouen, 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), Institut Gustave Roussy (IGR), CHU Toulouse [Toulouse]-Hôpital Larrey [Toulouse], CHU Toulouse [Toulouse], Service de Pneumologie - Oncologie Thoracique - Maladies Pulmonaires Rares [CHU Tenon], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Hôpital Charles Nicolle [Rouen]-CHU Rouen |
| المصدر: | Annals of Oncology Annals of Oncology, 2019, 30 (12), pp.1985-1991. ⟨10.1093/annonc/mdz407⟩ Annals of Oncology, Elsevier, 2019, 30 (12), pp.1985-1991. ⟨10.1093/annonc/mdz407⟩ |
| بيانات النشر: | HAL CCSD, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Oncology, Male, Oncogene Proteins, Fusion, medicine.medical_treatment, [SDV]Life Sciences [q-bio], ROS1 fusion, Phases of clinical research, Targeted therapy, 0302 clinical medicine, Carcinoma, Non-Small-Cell Lung, Molecular Targeted Therapy, Aged, 80 and over, Gene Rearrangement, Hematology, Middle Aged, Protein-Tyrosine Kinases, Proto-Oncogene Proteins c-met, targeted therapy, Progression-Free Survival, 3. Good health, 030220 oncology & carcinogenesis, Cohort, Female, medicine.drug, Adult, medicine.medical_specialty, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Disease-Free Survival, 03 medical and health sciences, Internal medicine, Proto-Oncogene Proteins, medicine, ROS1, Humans, Lung cancer, Protein Kinase Inhibitors, Aged, crizotinib, Crizotinib, business.industry, c-MET-mutation, Cancer, medicine.disease, c-MET amplification, Clinical trial, lung cancer, 030104 developmental biology, Mutation, business |
| الوصف: | Background In 2013, the French National Cancer Institute initiated the AcSe program to provide patients with secure access to targeted therapies outside of their marketed approvals. Efficacy and safety was then assessed using a two-stage Simon phase II trial design. When the study design was designed, crizotinib was approved only as monotherapy for adults with anaplastic lymphoma kinase plus non-small-cell lung cancers (NSCLC). Patients and methods Advanced NSCLC patients with c-MET ≥6 copies, c-MET-mutated, or ROS-1-translocated tumours were enrolled in one of the three cohorts. Patients were treated with crizotinib 250 mg twice daily. Efficacy was assessed using the objective response rate (ORR) after two cycles of crizotinib as primary outcome. Secondary outcomes included disease control rate at four cycles, best ORR, progression-free survival, overall survival, and drug tolerance. Results From August 2013 to March 2018, 5606 patients had their tumour tested for crizotinib targeted molecular alterations: 252 patients had c-MET ≥6 copies, 74 c-MET-mutation, and 78 ROS-1-translocated tumour. Finally, 25 patients in the c-MET ≥6 copies cohort, 28 in the c-MET-mutation cohort, and 37 in the ROS-1-translocation cohort were treated in the phase II trial. The ORR was 16% in the c-MET ≥6 copies cohort, 10.7% in the mutated, and 47.2% in the ROS-1 cohort. The best ORR during treatment was 32% in the c-MET-≥6 copies cohort, 36% in the c-MET-mutated, and 69.4% in the ROS-1-translocation cohort. Safety data were consistent with that previously reported. Conclusions Crizotinib activity in patients with ROS1-translocated tumours was confirmed. In the c-MET-mutation and c-MET ≥6 copies cohorts, despite insufficient ORR after two cycles of crizotinib, there are signs of late response not sufficient to justify the development of crizotinib in this indication. The continued targeting of c-MET with innovative therapies appears justified. Clinical trial number NCT02034981. |
| اللغة: | English |
| تدمد: | 0923-7534 1569-8041 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::487217358f47df224fa568af23e7e11cTest https://hal.science/hal-02530381Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....487217358f47df224fa568af23e7e11c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 09237534 15698041 |
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