Initial phase II results with crizotinib in advanced <i>ALK</i>-positive non-small cell lung cancer (NSCLC): PROFILE 1005.

Abstract

7514 Background: The anaplastic lymphoma kinase (ALK) fusion gene is a key oncogenic driver in a subset of NSCLC patients (pts). Crizotinib is a potent, selective, ATP-competitive, small molecule ALK inhibitor. Pts with ALK-rearranged NSCLC had a high response rate to crizotinib in a prior expanded cohort study. Methods: This ongoing study included pts from 57 sites in 12 countries with ALK-rearranged NSCLC (by centralized FISH test) who progressed after ≥1 chemotherapy for recurrent/advanced/metastatic disease (including treated brain metastases). Pts received oral crizotinib 250 mg BID continuously in 3-week cycles. Disease response was evaluated by RECIST 1.1 every 6 weeks and safety/patient-reported outcomes (PRO; by EORTC QLQ-C30/QLQ-LC13 v3) were evaluated every 3 weeks. Results: Currently, 136 pts are evaluable for safety, 109 for PRO, and 76 for tumor response. Median age was 52 years, 94% had adenocarcinoma, 68% had never smoked, and 53% were female. Most pts (93%) had ≥2 prior chemotherapy regimens (range 1–11). Pts 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 pts, 63 of 76 pts (83%) had target lesion shrinkage (41 pts had ≥30% shrinkage). Seven patients experienced objective progression by RECIST. The most frequent treatment-related AEs were nausea (46%), vision disorder (45%), vomiting (39%), and diarrhea (29%), mostly Grade 1/2. Treatment-related Grade 3/4 AEs were reported in 15% of pts (mostly increased ALT, dyspnea, and neutropenia). Two of the 9 deaths on-study were considered treatment-related (pneumonitis, unknown cause). Most pts had completed 4 PRO assessments by this review, with clinically significant (≥10 points) improvements in pain, cough, dyspnea and fatigue seen as early as cycle 2. Only a clinically significant increase in constipation was reported by patients over the course of therapy. Overall, quality of life was maintained. Conclusions: Data from a second global clinical study suggest crizotinib was safe and well-tolerated with preliminary evidence of improved symptoms and clinically meaningful antitumor activity in pts with pre-treated ALK-rearranged NSCLC.