Initial Phase 2 Results of Crizotinib Show Promise in Advanced ALK-Positive NSCLC

CHICAGO—Data from an international, multicenter, open-label, Phase 2 clinical study suggested that crizotinib was safe and well-tolerated with preliminary evidence of improved symptoms and clinically meaningful antitumor activity in patients with pretreated ALK-rearranged metastatic non-small cell lung cancer (NSCLC), investigators reported during the American Society of Clinical Oncology's 2011 Annual Meeting.

Disease response was evaluated by RECIST 1.1 (Response Evaluation Criteria in Solid Tumors) every 6 weeks and safety/patient-reported outcomes (PRO; by EORTC quality of life questionnaires: QLQ-C30/QLQ-LC13 v3) were evaluated every 3 weeks.

This ongoing study conducted by Lucio Crinó, MD, Ospedale Santa Maria della Misericordia, Perugia, Italy, and colleagues included patients from 151 sites in 22 countries with ALK-rearranged NSCLC (by centralized FISH test) who progressed after ≥1 platinum-based chemotherapy for recurrent/advanced/metastatic disease (including treated brain metastases). Patients received oral crizotinib 250mg twice daily continuously in 3-week cycles. Currently, 136 patients are evaluable for safety, 109 for PRO, and 76 for tumor response.

Median age in the study was 52 years (range, 28–82), 95.6% had adenocarcinoma, 67.6% had never smoked, and 53% were female. Most patients (93%) had ≥2 prior chemotherapy regimens (range 1–9). Patients received a median 9 weeks of treatment (range 1–13 cycles started) and 88% remain on therapy.

On a waterfall plot of tumor measurements in evaluable patients, 63 of 76 pts (83%) had target lesion shrinkage (41 patients had ≥30% shrinkage). Objective response rate (complete response + partial response) was 51.1% (63/133 evaluable patients), 95% CI [42.3–59.9]. Of those patients with a response, 79.4% (54/68) had a response within the first 8 weeks of treatment; median time to response was 6.1 weeks (range, 5.1–24.3). Seven patients experienced objective progression by RECIST.

Grade 1/2 gastrointestinal adverse events (AEs) were the most commonly reported and included nausea (50%), vomiting (39%), and diarrhea (39.7%). Vision disorder also occurred in 56.6% of patients. Grade 3/4 AEs were reported in 15% of patients and included increased ALT, dyspnea, and neutropenia. Nine deaths were reported and two were considered treatment-related (pneumonitis; unknown cause).

Approximately 56% of patients had completed eight cycles of PRO assessments by this review, with clinically significant (≥10 points) improvements in pain, cough, dyspnea and fatigue seen as early as cycle 2 that were maintained during treatment. Only a clinically significant increase in constipation was reported by patients over the course of therapy. Global QoL was maintained over therapy with clinically meaningful improvement at Cycle 7.

 Dr. Crinó, MD et al conclude that crizotinib appears to be safe and well-tolerated with preliminary evidence of improved symptoms and clinically meaningful antitumor activity in patients with pre-treated ALK-rearranged NSCLC.