ALK fusion variants could influence NSCLC crizotinib response

By Shreeya Nanda

In non-small-cell lung cancer (NSCLC) patients with anaplastic lymphoma kinase (ALK) rearrangement treated with crizotinib, progression-free survival (PFS) varies according to the ALK fusion variant.

ALK gene rearrangements result in the formation of the EML4-ALK fusion oncogene, the variants of which differ on the basis of which exon of EML4 is fused to ALK exon 20, explain Tatsuya Yoshida and co-workers, from Aichi Cancer Center Hospital in Japan, who explored the link between the ALK fusion variants and response to crizotinib.

Among 55 patients given the ALK tyrosine kinase inhibitor, median PFS was 11.0 months for the 54% of patients with ALK variant 1 (with exon 13 of EML4). This was significantly longer than the 4.2 months for the remaining participants who harboured ALK variants other than variant 1.

And in multivariate analysis, the presence of variant 1 and advanced stage were the only two factors significantly associated with PFS duration, with the former exerting a positive and the latter a negative effect (hazard ratios of 0.350 and 4.646, respectively).

"Therefore, the treatment strategy for ALK-positive NSCLC should be determined on the basis of the ALK variant status of the patient", Yoshida et al conclude in the Journal of Clinical Oncology.

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