Approximately 3–5% of NSCLC harbors ALK gene rearrangements. Crizotinib is a first-in-class, oral, small-molecule competitive ALK inhibitor with anti-MET activity.Methods
PROFILE 1005 is an ongoing global, multicenter, open-label, single-arm, phase II study evaluating the safety and efficacy of crizotinib (250 mg bid in 3-week cycles) in patients with advanced ALK-positive NSCLC who progressed after ≥1 chemotherapy for recurrent/advanced/metastatic disease. The tumor response was evaluated by RECIST 1.1 every 6 weeks. Patient-reported symptoms and global quality of life (QOL) were assessed using the EORTC QLQ-C30 and LC-13 at baseline, day 1 each cycle and at the end of treatment.Results
As of June 2011, 439 patients were evaluable for safety and 255 patients for tumor response. Median age was 53 years. The majority of patients were female (53%), never smokers (65%), and had adenocarcinoma (92%), ECOG PS 0–1 (83%) and ≥2 prior chemotherapy regimens (85%). Among patients evaluable for efficacy, the median treatment duration was 25 weeks (77% of patients still ongoing). ORR was 53% (95% CI: 47–60), disease control rate at 12 weeks was 85% (95% CI: 80–89), the median duration of response was 43 weeks (96% CI 36–50) and median PFS was 8.5 months (95% CI: 6.2–9.9). The most frequent treatment-related AEs were visual effects (50%), nausea (46%), vomiting (39%), and diarrhea (35%), mostly grade 1–2. Twenty-nine patients (6.6%) had treatment-related SAEs, including dyspnea and pneumonitis (four patients each; 0.9%), and febrile neutropenia and renal cyst (two patients each; 0.5%). A statistically significant (P < 0.05) and clinically meaningful (≥10 points) improvement from baseline was observed for patient-reported overall pain, pain in chest, cough, dyspnea, insomnia, fatigue and global QOL.Conclusions
Crizotinib demonstrated a high response rate and PFS, favorable tolerability profile and improvement in patient-reported symptoms. These results provide strong evidence for crizotinib as a standard of care for advanced ALK-positive NSCLC.