First-Line Selpercatinib in RET Fusion-Positive NSCLC

RET fusions occur in 1% to 2% of non–small-cell lung cancers (NSCLCs), usually in young light or never smokers with adenocarcinoma histology, and are associated with a high incidence of central nervous system (CNS) metastases. Selpercatinib is a highly potent RET inhibitor that has demonstrated significant efficacy in phase 1 and 2 trials of RET fusion-positive NSCLC.

Now, researchers report an interim analysis of an industry-sponsored, open-label, phase 3 trial in which 261 patients with RET fusion-positive NSCLC were randomized to receive selpercatinib (160 mg twice daily; n=159) or investigator's choice of platinum-based chemotherapy plus pemetrexed with or without pembrolizumab (n=102).

The intention-to-treat (ITT) pembrolizumab population (patients whose physicians would have treated them with pembrolizumab had they been randomized to the chemotherapy arm) included 129 patients who received selpercatinib and 83 who received chemotherapy plus pembrolizumab. The median progression-free survival (PFS) in the ITT-pembrolizumab population was 24.8 months with selpercatinib versus 11.2 months with chemotherapy plus pembrolizumab (hazard ratio, 0.46; P<0.001). Results were similar in the overall ITT population (all randomized patients), which suggests no additional benefit of upfront immunotherapy in this population. Response rates were improved with selpercatinib compared with the ITT pembrolizumab control (84% vs. 65%), and the time to CNS progression was longer (HR, 0.28). No new safety signals were noted.