Dr. Gandara on TS Expression in ALK-Positive NSCLC

David R. Gandara, MD, Director, Thoracic Oncology Program, University of California, Davis Comprehensive Cancer Center, discusses a database analysis conducted by the Southwest Oncology Group (SWOG) that examined the possible connection between thymidylate synthase (TS) expression and ALK-positivity in patients with non-small cell lung cancer (NSCLC).

A connection between ALK-positive NSCLC and TS, a predictive marker for sensitivity to the chemotherapeutic agent pemetrexed, could impact the way that patients with ALK-positive NSCLC are treated.

In order to establish a connection, the study examined 1,761 patients with lung adenocarcinoma that did not have an EGFR or KRAS mutation, from the Response Genetics Inc. (RGI) database. In total, 63 of the patients were ALK-positive and 1698 were negative. The median TS RNA level for patients with an ALK-positive tumor was 2.02 compared to 3.32 for ALK-negative. In general, TS levels less than 2.33 denote sensitivity to pemetrexed.

Gandara believes that this analysis provides a biologic rationale for the reports that pemetrexed is active in ALK-positive NSCLC. Following the positive results of the proof of concept analysis, SWOG plans to conduct a larger randomized trial that will provide patients with ALK-positive NSCLC either pemetrexed alone or in combination with the ALK-targeted agent crizotinib (Xalkori).