Progression-free survival (PFS) from a phase I study of crizotinib (PF-02341066) in patients with ALK- positive non-small cell lung cancer (NSCLC).

Abstract

Background: The anaplastic lymphoma kinase (ALK) fusion gene is a key oncogenic driver in a subset of patients with NSCLC. Crizotinib is a potent and selective, ATP-competitive, small molecule ALK inhibitor. Patients with ALK-positive NSCLC may benefit from targeted ALK inhibitors. Methods: An ongoing open-label, multicenter, 2-part, phase I trial is investigating the safety, tolerability, pharmacokinetics, and antitumor activity of crizotinib in patients with advanced cancer. Updated safety and response data and preliminary PFS data from an expanded ALK-positive cohort of patients with NSCLC in part 2 of the study are reported. Patients received oral crizotinib 250 mg BID in 28-day cycles. Results: Currently, 119 patients with ALK-positive NSCLC have enrolled and 116 are evaluable for response, with 94 in follow-up for survival. Median age was 51 years; patients were usually never- or former-smokers (99%) with adenocarcinoma histology (97%). Most patients were heavily pretreated, with 44% receiving ≥3 prior treatments. At a median follow-up of 11 months (95% CI: 9.2, 12.8 months), ORR was 61% (95% CI: 52%, 70%), including 2 CRs and 69 PRs, and clinical benefit rate (CR+PR+SD) was 88%. Responses (CR or PR) were rapid (median 8 weeks to response). Preliminary median response duration estimate was 48 weeks (95% CI: 36 weeks, not reached). Preliminary median PFS was 10 months (95% CI: 8, 15 months). Median OS has not been reached. Treatment-related AEs were mostly Grade 1/2 with vision disorder (63%) and GI events (nausea, 54%; diarrhea, 49%; vomiting, 40%) the most common. These AEs typically had an early onset (Cycle 1) and diminished as treatment continued. Conclusions: In patients with ALK-positive NSCLC, the efficacy of crizotinib was robust, rapid, durable and clinically meaningful. The most common AEs with crizotinib were either self-limiting or easily managed. Crizotinib may offer a new standard of care for patients with ALK-positive advanced NSCLC, a subgroup that currently lacks any approved agent specific to the molecular diagnosis.