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|Ref Type||Journal Article|
|Authors||Moro-Sibilot D, Cozic N, Pérol M, Mazières J, Otto J, Souquet PJ, Bahleda R, Wislez M, Zalcman G, Guibert SD, Barlési F, Mennecier B, Monnet I, Sabatier R, Bota S, Dubos C, Verriele V, Haddad V, Ferretti G, Cortot A, De Fraipont F, Jimenez M, Hoog-Labouret N, Vassal G|
|Title||Crizotinib in c-MET- or ROS1-positive NSCLC: results of the AcSé phase II trial.|
|Journal||Annals of oncology : official journal of the European Society for Medical Oncology|
|Date||2019 12 01|
|Abstract Text||In 2013, the French National Cancer Institute initiated the AcSé 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).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.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.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.NCT02034981.|
|Molecular Profile||Treatment Approach|
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|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|ROS1 rearrange||lung non-small cell carcinoma||sensitive||Crizotinib||Phase II||Actionable||In a Phase II trial (AcSe), treatment with Xalkori (crizotinib) resulted in a an overall response rate after 2 cycles of 47.2% (17/36; all partial responses), and after 4 cycles resulted in a best overall response rate of 69.4% (21/36; 20 partial responses and 1 complete response), and a median progression-free survival of 5.5 months and median overall survival of 17.2 months in patients with ROS1-translocated non-small cell lung cancer (PMID: 31584608; NCT02034981).||31584608|