ALK Variant 1 Confers Better Efficacy With Crizotinib in NSCLC
Crizotinib may be clinically beneficial for patients with non-small cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) variant 1.
Crizotinib may be clinically beneficial for patients with non-small cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) variant 1, as opposed to other variants, according to a study published in the Journal of Clinical Oncology.1
ALK rearrangement-positive NSCLC can be treated with an ALK tyrosine kinase inhibitor, such as crizotinib, ceritinib, and alectinib, though the response magnitude and duration are mixed. Because several variants in ALK have been identified, researchers evaluated the impact of different ALK variants on the efficacy of crizotinib in patients with ALK mutation-positive NSCLC.
Investigators analyzed data from 35 patients treated with crizotinib as the initial ALK kinase inhibitor between 2007 and 2014. ALK variants were assessed via reverse transcription polymerase chain reaction; efficacy of crizotinib was retrospectively evaluated on the basis of objective response rate and progression-free survival with respect to ALK variants.
Researchers found that the most common ALK variant was variant 1, which was found in 54% of patients, followed by variant 2 in 14%, variant 3a/3b in 12%, and other variants observed in 20%.
Results showed that objective response rate was 69% among all patients, but was 74% in the variant 1 group versus 63% in non-variant 1 groups. Median progression-free survival was 11.0 months (95% CI, 6.5-43.0), compared with 4.2 months (95% CI, 1.5-10.2), respectively (P < .05).
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The study demonstrated that ALK variant 1 (hazard ratio, 0.350; 95% CI, 0.128-0.929) and advanced stage of cancer (hazard ratio, 4.646; 95% CI, 1.381-21.750) were significantly associated with median progression-free survival (P < .05).
- Yoshida T, Oya Y, Tanaka K, Shimizu J, Horio Y, Kuroda H, et al. Differential crizotinib response duration among ALK fusion variants in ALK-positive non–small-cell lung cancer [published online ahead of print June 27, 2016]. J Clin Oncol. doi: 10.1200/JCO.2015.65.8732.