Dr. Drilon on Rare Drivers in NSCLC

Alexander E. Drilon, MD, medical oncologist at Memorial Sloan Kettering (MSK) Cancer Center, discusses rare drivers in non—small cell lung cancer (NSCLC).

There are several other emerging biomarkers in addition to MET activation, explains Drilon. RET fusions, for example, are found in up to 2% of patients with NSCLC. Although older multikinase inhibitors showed modest activity, there were issues with tolerability.

Since then, more selective RET inhibitors have been introduced into the clinic. These include BLU-667 and LOXO-292, both of which show high tolerability and response rates ranging from 50% up to 70%. In September 2018, LOXO-292 received a breakthrough therapy designation from the FDA for the treatment of patients with RET fusion—positive NSCLC. The agent also holds designations for advanced RET fusion—positive thyroid cancer and RET-mutant medullary thyroid cancer.

There are also NTRK fusions or rearrangements, which are found at a high frequency in some rare cancers, such as salivary cancers or breast cancers, but also at a lower frequency across other solid tumors, like lung cancers, says Drilon. Two first-generation TRK inhibitors are now in development: entrectinib and larotrectinib (Vitrakvi), updates on both of these agents were presented at the 2018 ESMO Congress. Across any solid tumor that harbors an NTRK fusion, investigators reported a response rate of about 57% with entrectinib, while updated data with larotrectinib showed a response rate of about 80%.