Crizotinib shows antitumor activity in ROS1-positive NSCLC

Crizotinib proves to be effective against nonsmall-cell lung cancer (NSCLC) with ROS-1 translocations and has modest activity in c-MET >6 copies and c-MET mutations, according to the results of the phase II AcSé trial.

Of the 5,606 NSCLC patients whose tumour samples were tested, 404 were found to have biomarker positive malignancy: 252 (6.0 percent) with c-MET ≥6 copies, 74 (6.2 percent) with c-MET-mutated and 78 (1.9 percent) with ROS-1- translocations tumours.

A total of 90 patients were then included and treated in the phase II trial: 25 in the c-MET ≥6 copies cohort, 28 in the c-MET-mutation cohort and 37 in the ROS-1-translocation cohort. All patients received 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.

The primary outcome of objective response rates (ORRs) after two cycles of treatment were 16 percent in the c-MET ≥6 copies cohort, 10.7 percent in the mutated c-MET cohort and 47.2 percent in the ROS-1 cohort.

The best ORRs during treatment were 32 percent in the c-MET ≥6 copies cohort, 36 percent in the c-MET mutated cohort and 69.4 percent in the ROS-1 translocation cohort at four cycles. Corresponding disease control rates were 52 percent, 39 percent and 69.4 percent.

The median progression-free survival and overall survival were 3.2 and 7.7 months in the c-MET ≥6 copies cohort, 2.4 and 8.1 months in the c-MET mutated cohort, and 5.5 and 17.2 months in the ROS-1 translocation cohort.

Researchers noted signs of late activity in the c-MET mutation and c-MET ≥6 copies cohorts, although the response was not sufficient to justify the development of crizotinib in this indication.

The safety profile of crizotinib was consistent with that previously reported, being associated with mostly grade ≤2 adverse events.