(CHICAGO, IL) – Crizotinib has a strong response rate, progression-free survival (PFS), and is well tolerated in patients with ALK-positive non-small cell lung cancer (NSCLC), according to results of a Phase 2 study presented at the 2012 American Association of Clinical Oncology Annual Meeting.

Crizotinib is a first-in-class, oral, small-molecule, competitive ALK inhibitor with anti-MET activity, explained lead author Dong-Wan Kim, MD, PhD, of Seoul National University Hospital, Seoul, South Korea. Dr. Kim added that approximately 3% to 5% of NSCLC harbors ALK gene rearrangements, and that these rearrangements are predominantly found in adenocarcinomas. PROFILE 1005 is an ongoing global, multicenter, open-label, single-arm, Phase 2 study designed to evaluate the safety and efficacy of crizotinib in patients with advanced ALK-positive NSCLC.

Patients whose disease had progressed despite being treated with at least one form of chemotherapy for recurrent, advanced, metastatic disease were eligible to receive oral crizotinib (250mg, twice daily, in 3-week cycles). Tumor response, patient-reported symptoms, and global quality of life (QOL) were assessed.

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At the data cutoff on January 2, 2012, a total of 901 patients had received treatment with crizotinib; the mature population included the first 261 patients enrolled and treated in the study as of February 1, 2011. Among the mature population, median treatment duration was 48 weeks. Overall response rate (ORR) was 59.8% (95% CI: 53.6–65.9), 4 complete responses and 151 partial responses; median duration of response was 45.6 weeks (96% CI: 35.3–53.6). Of those patients with a response, 71% had a response within the first 8 weeks of treatment and median time to response was 6.1 weeks (range, 4.9–49.1). Median PFS was 8.1 months (95% CI: 6.9–9.7).

In the mature population, the most frequent treatment-related adverse events (AEs) were primarily grade 1–2 visual effects (59%), nausea (56.7%), vomiting (44.4%), and diarrhea (40.6%). Treatment-related AEs grade ≥3 were reported in 25.6% of patients, most frequently neutropenia (5.5%), increased alanine aminotransferase (4.0%), and fatigue (2.0%). Five patients discontinued treatment due to increased alanine aminotransferase and eight due to pneumonitis, with rare instances of fatal pneumonitis reported. Four of 198 deaths during the study were considered treatment-related by the investigators.

A statistically significant (P<0.05) and clinically meaningful (≥10 points) improvement from baseline was observed for patient-reported overall pain, chest pain, arm and shoulder pain, cough, dyspnea, fatigue, and global QOL.

Dr. Kim and colleagues concluded that “crizotinib continues to have a good safety profile in patients with previously treated ALK-positive advanced NSCLC, with clinically meaningful anti-tumor activity.”