• Among 16 patients, cabozantinib demonstrated an ORR of 38%, a median PFS of 7 months and a median OS of 10 months.
• Although cabozantinib-associated adverse events were frequent, they were mostly Grade 1 or Grade 2.

The reported frequency of RET rearrangements — one of the newest targets in the systemic treatment of NSCLC — is 1% to 2%, although Dr Spigel and others believe that with more sensitive assays this number could be higher and probably exceeds the frequency of ROS1 rearrangements. Cabozantinib is a multikinase inhibitor approved for the treatment of progressive metastatic medullary thyroid cancer that in addition to targeting MET and VEGF receptors 1 through 3 also interferes with RET.

At this early phase of development responses seem durable, with a median OS of 10 months. Many patients require dose adjustment because of toxicity such as fatigue, and as with many TKIs careful monitoring of side effects is necessary to maintain quality of life.