Multinational phase 3 trial of first-line selpercatinib or chemotherapy and pembrolizumab for RET fusion-positive non-small cell lung cancer

Selpercatinib is a highly selective potent and brain-penetrant RET inhibitor. The multinational phase 3 LIBRETTO-431 trial compared first-line selpercatinib versus chemotherapy with or without pembrolizumab (at the investigator’s discretion) for RET fusion-positive NSCLC. At the time of the now published preplanned interim analysis the progression-free survival (primary end point) was 24.8 months with selpercatinib versus 11,2 months with control. The percentage of patients with objective response was 84% with selpercatinib versus 65% with control. The cause-specific hazard ratio for the time to progression affecting the central nervous system was 0.28 (95%-bti 0.12-0.68). Efficacy results in the overall intention-to-treat population were similar to those in the intention-to-treat-pembrolizumab population. Adverse events were consistent with what has been previously reported. The authors conclude that treatment with selpercatinib led to significantly longer progression-free survival than treatment with chemotherapy with or without pembrolizumab.