Impact of crizotinib on survival in patients with advanced, ALK-positive NSCLC compared with historical controls.

Abstract

7507 Background: ALK represents one of the newest tyrosine kinase targets in lung cancer. In a seminal phase I trial, the ALK tyrosine kinase inhibitor crizotinib showed marked antitumor activity in patients with advanced, ALK+ NSCLC. However, in the absence of randomized data, the impact of crizotinib on overall survival (OS) of these patients is not known. Methods: We examined survival of 82 ALK+ patients who enrolled in the expansion cohort of the phase I trial of crizotinib (Kwak et al., NEJM, 2010). For comparators, we identified 37 ALK+ patients from phase I sites who were not treated with crizotinib (ALK+ controls), as well as 253 ALK-/EGFR- patients from one site (ALK- controls). All ALK+ and ALK- controls had advanced NSCLC. Results: In 82 ALK+ patients treated with crizotinib, 1-yr OS was 77% and 2-yr OS was 64%; median (med) OS has not been reached (NR). OS did not differ based on sex (p=0.35), ethnicity (Asian vs non-Asian, p=0.46), smoking history (never vs any smoking, p=0.82) or age (< or > 60 yrs, p=0.93). Among the 37 ALK+ controls, 1- and 2-yr OS was 73% and 33%, respectively, and med OS was 20 mos. As ALK+ controls were identified at sites outside of Korea, we compared controls with the non-Korean cohort of crizotinib-treated patients (n=56). Both groups were similar in age (median 51 vs 51, p=0.97), sex (57% vs 46% F, p=0.40), smoking history (68% vs 79% neversmokers, p=0.33), presence of brain mets at any time (49% vs 48%, p=1.00), number of prior therapies (mean 2.05 vs 2.09, p=0.17), and types of prior chemotherapy. We examined subsets of ALK+ patients by line of therapy. Survival of 32 patients treated with 2nd /3rd line crizotinib was significantly longer than that of 24 ALK+ controls (p=0.004): 1-yr OS was 71% vs 46%, 2-yr OS was 61% vs 9%, and med OS was NR vs 11 mos for the subset of crizotinib-treated patients vs the subset of ALK+ controls, respectively. For 123 ALK- controls in the 2nd line setting, the 1- and 2-yr OS was 49% and 33%, respectively, and the med OS was 11 mos. Conclusions: In patients with ALK+ NSCLC, crizotinib therapy is associated with a higher OS than that of historical, crizotinib-naïve controls. We propose that crizotinib represents a new standard of care for patients with ALK+ NSCLC.