IS7-14 - Results of a GlobaL Phase II Study with Crizotinib in Advanced ALK-Positive Non-Small-Cell Lung Cancer (NSCLC)

Abstract

ABSTRACT Background Anaplastic lymphoma kinase (ALK) is a known oncogenic driver in NSCLC, and approximately 5% of patients harbor ALK gene rearrangements. Crizotinib is a first-in-class, selective small-molecule ALK inhibitor with demonstrated clinical activity in ALK-positive NSCLC. PROFILE 1005 is a global, multicenter, open-label, single-arm phase II study evaluating the safety and efficacy of crizotinib in previously treated patients with ALK-positive advanced NSCLC. Methods Crizotinib 250 mg was administered BID to patients with ALK-positive advanced NSCLC who had received ≥1 chemotherapy for locally advanced/metastatic disease, including those with treated brain metastases. Most patients had centrally confirmed ALK-positivity by break-apart fluorescence in-situ hybridization, defined as ≥15% of tumor cells with split signals. Disease response was evaluated by RECIST 1.1 every 6 weeks. Results As of January 2012, 901 patients had been dosed. The first 261 patients who had enrolled and started crizotinib by February 2011, with a median duration of treatment of 48 weeks, were considered to be the mature population. Demographic, exposure, and efficacy results in both the overall and mature populations are provided in the table. Among all 901 patients, 15% discontinued treatment due to adverse events (AEs) and 10% had a dose reduction due to an AE. The most frequent AEs of any cause were vision disorder (54%), nausea (51%), diarrhea (44%), vomiting (44%), and constipation (37%), which were mostly grade 1/2. Conclusions Crizotinib demonstrated a high response rate that was durable, with a median progression-free survival of 8.1 months. Crizotinib has a favorable tolerability profile. These findings continue to provide strong evidence for crizotinib as a standard of care for advanced ALK-positive NSCLC. Overall population Mature population Total no. of patients, n 901 261 Response-evaluable patients, n 803 259 Demographics: Median age, years Male/female, % ECOG PS 0/1, % Adenocarcinoma, % 53 43/57 82 92 52 46/54 83 94 Duration of treatment (weeks), median (range) 20 ( 48 (1 - 94) ORR, % (95% exact CI) 46 (42–50) 60 (54–66) Duration of response (weeks), median a (95% CI) 47 (36–54) 46 (35–54) Disease control rate, % (95% exact CI): At 6 weeks At 12 weeks 80 (77–83) 61 (58–64) 86 (82–90) 75 (70–80) PFS (months), median a (95% CI) 8.1 (6.9–9.5) 8.1 (6.8–9.7) ECOG PS, Eastern Cooperative Oncology Group performance status; ORR, objective response rate; PFS, progression-free survival. a Kaplan–Meier estimate Disclosure D. Kim: Compensated advisory relationship: Pfizer. Honoraria: Pfizer. S. Lanzalone: Employment: Pfizer. Stock ownership: Pfizer. A. Polli: Employment: Pfizer. Stock ownership: Pfizer. A. Shaw: Compensated advisory relationship: Pfizer, Ariad, Chugai, Novartis, Daiichi-Sankyo. Research funding: AstraZeneca, Novartis. All other authors have declared no conflicts of interest.