Response to Cabozantinib in Patients with RET Fusion-Positive Lung Adenocarcinomas

We report preliminary data for the first three patients treated with the RET inhibitor cabozantinib on a prospective phase II trial for patients with RET fusion-positive NSCLCs (NCT01639508). Confirmed partial responses were observed in 2 patients, including one harboring a novel TRIM33RET fusion. A third patient with a KIF5BRET fusion has had prolonged stable disease approaching 8 months (31 weeks). All three patients remain progression-free on treatment.

This report of the activity of cabozantinib in RET fusion-positive disease provides early clinical validation of RET fusions as drivers in lung cancers and suggests that RET inhibition may represent a new treatment paradigm in this molecular cohort.