Variant ALK Rearrangements Alter NSCLC Crizotinib Outcomes

Differences in anaplastic lymphoma kinase rearrangements are linked to non-small-cell lung cancer progression-free survival after crizotinib

medwireNews: Variant forms of the anaplastic lymphoma kinase (ALK) rearrangement may influence non-small-cell lung cancer (NSCLC) response to the ALK tyrosine kinase inhibitor crizotinib , Japanese research suggests.

Tatsuya Yoshida and co-workers, at the Aichi Cancer Center Hospital in Nagoya, describe the outcomes of 35 patients undergoing crizotinib therapy for ALK-rearranged NSCLC between 2007 and 2014.
Nineteen of the patients had variant 1 rearrangement, five had variant 2 and four had variant 3a/3b. The remaining seven patients each had a different variant form of the rearrangement, the team reports in the Journal of Clinical Oncology.

Patients with ALK variant 1 were significantly more likely to achieve disease control – defined as a complete or partial response, or stable disease – than those with non-variant 1 arrangements, at 95% versus 63%.
The patients had an overall median progression-free survival (PFS) of 9.7 months but those with a variant 1 rearrangement had significantly longer PFS than patients with other forms, at 11.0 versus 4.2 months.

And multivariate analysis confirmed that PFS was significantly and independently predicted by ALK variant 1 and advanced stage disease, with hazard ratios of 0.35 and 4.65, respectively, the authors say.

Progressive disease occurred in 25 patients, most commonly affecting the central nervous system, but patients with variant 1 and non-variant 1 rearrangements had comparable rates of central nervous system, intrathoracic and extrathoracic recurrence.

The researchers note that patients with and without variant 1 rearrangements had a comparable need for treatment interruption or dose reduction, and none permanently discontinued treatment because of side effects.

The team suggests that the “treatment strategy for ALK-positive NSCLC should be determined on the basis of the ALK variant status of the patient.”

“Further multicenter, prospective studies will need to be performed to confirm the specific association between the ALK variant status and efficacy of crizotinib”, they say.

Reference

Yoshida T, Oya Y, Tanaka K, et al. Differential crizotinib response duration among ALK fusion variants in ALK-positive non-small-cell lung cancer. J Clin Oncol 2016; Advance online publication 27 June. doi: 10.1200/JCO.2015.65.8732

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