Crizotinib vs chemotherapy in ALK+ advanced non-small cell lung cancer (NSCLC): Final survival results from PROFILE 1007.

9066 Background: PROFILE 1007 demonstrated superior PFS with crizotinib vs standard-of-care chemotherapy in patients (pts) with ALK+ advanced NSCLC previously treated with 1 prior platinum-based regimen. Here, we present final OS and updated safety data from this study. Methods: In this ongoing open-label phase 3 trial (NCT00932893), pts were randomized (1:1) to crizotinib 250 mg PO BID or chemotherapy (pemetrexed 500 mg/m2 or docetaxel 75 mg/m2, IV q3w). Pts with PD (per independent radiological review) on chemotherapy could cross over to crizotinib in a separate study. The Kaplan-Meier method was used to estimate OS, 1-sided stratified log-rank tests to compare survival curves, and stratified Cox regression models to estimate HRs. Results: 347 pts were randomized: 173 to crizotinib (172 treated), 174 to chemotherapy (171 treated). At data cutoff (Aug 31, 2015), 13 (8%) and 0 pts randomized to crizotinib and chemotherapy, respectively, were on treatment. Median treatment duration (range) was 48 wk (1–263) and 13 wk (3–162) and median duration of follow-up was 51.0 and 53.1 mo in the crizotinib and chemotherapy arms, respectively. There was a numerical, but not statistically significant, improvement in the secondary endpoint of OS for crizotinib vs chemotherapy (HR: 0.85; 95% CI: 0.66−1.10; P = 0.11; median 21.7 and 21.9 mo). 154 pts (89%) randomized to chemotherapy subsequently received crizotinib as follow-up systemic therapy. OS analysis with adjustment for crossover is in progress. The most common all-causality AEs (any grade) with crizotinib were diarrhea (62%), vision disorder (62%), and nausea (60%) and with chemotherapy were nausea (36%), fatigue (36%), and decreased appetite (27%). Grade 5 treatment-related AEs (TRAEs) were reported in 3 pts and 1 pt with crizotinib and chemotherapy, respectively. Treatment discontinuations associated with TRAEs were reported in 6% of pts on crizotinib and 12% on chemotherapy. Conclusions: In this randomized study, which allowed crossover to crizotinib, there was a numerical improvement in OS for crizotinib vs chemotherapy that did not reach statistical significance. Crizotinib has a distinct and generally tolerable safety profile. Clinical trial information: NCT02511184.