Lilly's Retevmo (selpercatinib) Phase 3 results in RET fusion-positive non-small cell lung cancer and RET-mutant medullary thyroid cancer both published in The New England Journal of Medicine and presented in a presidential symposium at ESMO Congress 2023

Eli Lilly and Company on 21 Oct 2023 announced results from both the LIBRETTO-431 Phase 3 study, which evaluated Retevmo (selpercatinib) versus platinum-based chemotherapy - with or without pembrolizumab - as an initial treatment for patients with advanced or metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC), and the LIBRETTO-531 Phase 3 study, which evaluated Retevmo versus multikinase inhibitors (MKIs) in patients with advanced or metastatic RET-mutant medullary thyroid cancer (MTC). In both clinical studies, results were based on pre-specified interim efficacy analyses conducted by independent data monitoring committees (IDMC). Results from the LIBRETTO-431 and LIBRETTO-531 Phase 3 trials were presented in a Presidential Symposium at the European Society for Medical Oncology (ESMO) Congress 2023 and simultaneously published in the New England Journal of Medicine. LIBRETTO-431 is a Phase 3, randomized, open-label trial that evaluated Retevmo in patients with advanced or metastatic, treatment-naive RET fusion-positive NSCLC. In the ITT-pembrolizumab population, the median PFS by BICR was 24.8 months with Retevmo versus 11.2 months in the control arm, corresponding to a hazard ratio (HR) of 0.465. PFS was longer with Retevmo than in the control arm across all pre-specified subgroups. The overall response rate (ORR) by BICR with Retevmo was 83.7% compared to 65.1% in the control arm. Similar results were observed in the ITT population in both BICR and investigator-assessed endpoints and across all pre-specified subgroups. Retevmo demonstrated superior PFS with an HR of 0.482 and an increase of more than 13 months in median PFS by BICR, showing 24.8 months with Retevmo versus 11.2 months with control. Overall survival (OS) results remain immature with a censoring rate of approximately 80% in the ITT-pembrolizumab arm. LIBRETTO-531 is a Phase 3, randomized, open-label trial that evaluated Retevmo versus physician's choice of MKIs cabozantinib or vandetanib, which are currently approved first-line options for patients with advanced or metastatic, kinase inhibitor-naive RET-mutant MTC. At the interim analysis, the study had met the criteria for positive PFS. At a median follow-up of approximately 12 months, the BICR-assessed median PFS in the Retevmo arm was not reached and remained inestimable, whereas the BICR-assessed median PFS in the control arm was 16.8 months. This corresponded to a HR of 0.280. Investigator-assessed PFS yielded similar results with an HR of 0.187. Both BICR and investigator-assessed PFS were longer with Retevmo across all pre-planned subgroups. Original source: Eli Lilly, website: http://www.lilly.com/, Copyright Eli Lilly and Company 2023.
research and development; anticancer drugs; cabozantinib; monoclonal antibodies; pembrolizumab; Retevmo; selpercatinib; vandetanib; Eli Lilly and [...]