The AcSé phase II study points out to crizotinib activity in patients with ROS1-translocated non-small cell lung cancer (NSCLC). In case of c-MET-mutation and c-MET ≥6 copies cohorts, despite insufficient overall response rate (ORR), there are signs of late response, but not sufficient to justify further research of crizotinib in this indication. The study results are published by Prof. Denis Moro-Sibilot of the Thoracic Oncology Unit, Grenoble-Alpes University Hospital in Grenoble, France and colleagues on 4 October 2019 in the Annals of Oncology.
The authors wrote that in 2013, the French National Cancer Institute initiated the AcSé programme to provide patients with secure access to targeted therapies outside of their marketed approvals.
At the time of study design, crizotinib was approved only as monotherapy for adult patients with ALK-positive NSCLC. A two-stage Simon phase II trial design was used. Patients with advanced NSCLC and c-MET ≥6 copies, c-MET-mutated, or ROS-1-translocated tumours were enrolled in one of the three study cohorts.
Crizotinib was administered 250 mg twice daily. Efficacy was assessed by 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, the study team tested tumours from 5606 patients for crizotinib matched targeted molecular alterations. There were 252 patients with c-MET ≥6 copies, 74 with c-MET-mutation, and 78 with ROS-1-translocated tumour. But only 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 finally treated in this phase II study.
The ORR was 16% in the c-MET ≥6 copies cohort, 10.7% in the c-MET-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.
The authors concluded that based on study results crizotinib activity is confirmed in NSCLC patients with ROS1-translocated tumours. However, continued research efforts are needed in terms of targeting c-MET with innovative therapies.
Moro-Sibilot D, Cozic N, Pérol M, et al. Crizotinib in c-MET- or ROS1-positive NSCLC: results of the AcSé phase II trial. Annals of Oncology; Published 4 October 2019. pii: mdz407. doi: 10.1093/annonc/mdz407.