ALK rearrangement–positive non-small lung cancers (NSCLC) can be effectively treated with ALK tyrosine kinase inhibitor (TKI) such as crizotinib. However, the magnitude and duration of response was heterogeneous. Several ALK variants have been identified, and there has been few reports focused on the influence of differential ALK variants on the efficacy of crizotinib. Therefore, the aim of this study was to evaluate whether ALK variants show differential efficacy to crizotinib.
Among 55 patients treated with crizotinib as initial ALK-inhibitor between January 2007 and December 2014, we identified 35 patients whose tumor specimens could be evaluated for ALK variants by reverse transcription polymerase chain reaction. Efficacies of crizotinib such as overall response rate (ORR), progression-free survival (PFS) were retrospectively evaluated according to ALK variants.
In ALK variant status, the most frequent variant was variant 1 in 19 (54%) patients, followed by variant 2 in 5 (14%), variant 3a/3 in 4 (11%), or others in 7 (17%). The ORR was 74 % in all patients, which included 74 % in the variant 1 group and 63% in non-variant 1 group respectively. The median PFS of all patients was 9.7 months. The median PFS was significantly longer in patients with variant 1 than those with non-variant 1 (median of 11.0 months [95% CI, 6.5-43.0 months], vs. 4.2 months [95% CI, 1.6-10.2months], P < 0.05). In multivariate analysis, we identified two significant factors associated with duration of PFS (ALK variant 1: HR 0.4260, 95% CI 0.184-0.984, P < 0.05, and advanced stage: HR 4.3817, 95% CI 1.394-19.583, P < 0.05).
Our data indicated better efficacy of crizotinib in variant 1 than non-variant1. ALK variant status may affect ALK-TKI.
Clinical trial identification
T. Hida: research funding and honoraria from Chugai Pharmaceutical, Pfizer and Novartis. All other authors have declared no conflicts of interest.