ROS1 Rearrangements Seen in Small Subset of NSCLC Tumors

Clinical features similar to those seen in ALK-rearranged non-small-cell lung cancer

MONDAY, Jan. 9 (HealthDay News) -- Approximately 2 percent of patients with non-small-cell lung cancer (NSCLC) have rearrangements of the ROS1 receptor tyrosine kinase gene, with clinical characteristics similar to those seen in ALK-rearranged NSCLC, according to a study published online Jan. 3 in the Journal of Clinical Oncology.

Kristin Bergethon, of the Massachusetts General Hospital in Boston, and colleagues investigated the clinical characteristics and treatment outcomes of the ROS1 rearrangement in 1,073 patients with NSCLC. Patients were screened using a fluorescent in situ hybridization (FISH) assay, and ROS1 rearrangement was correlated with clinical characteristics, overall survival, and ALK rearrangement status, when available. For cells with ROS1 rearrangement, in vitro studies were used to evaluate the responsiveness to the tyrosine kinase inhibitor crizotinib. As part of an expanded phase I cohort, the clinical response to crizotinib of one patient with ROS1 rearrangement was evaluated.

The researchers found that, based on FISH analysis, 1.7 percent of tumors exhibited ROS1 rearrangements and 2.9 were ALK rearranged. Patients with ROS1 rearrangements were significantly younger and more likely to be never-smokers compared with the ROS1-negative group. The ROS1-positive tumors were all adenocarcinomas and tended to be of a higher grade. Sensitivity to crizotinib was seen for the HCC78 ROS1-rearranged NSCLC cell line and in cells transfected with CD74-ROS1. The patient treated with crizotinib had a near complete response and demonstrated tumor shrinkage.

"ROS1 rearrangement defines a molecular subset of NSCLC with distinct clinical characteristics that are similar to those observed in patients with ALK-rearranged NSCLC," the authors write.

Several authors disclosed financial relationships with pharmaceutical companies, including Pfizer, which manufactures crizotinib and supported the crizotinib phase I trial.

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