Lessons from LIBRETTO-431 Trial in RET+ NSCLC

EP: 1.CheckMate 77T: Perioperative Immunotherapy in Resectable NSCLC

EP: 2.Evolving NSCLC Landscape: Comparing Recent Updates in Neoadjuvant and Perioperative Immunotherapy

EP: 3.Updates in ALK+ NSCLC: ALINA Trial at ESMO 2023

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EP: 4.Lessons from LIBRETTO-431 Trial in RET+ NSCLC

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EP: 6.Innovations Needed and Future Directions in Treatment of NSCLC

This is a video synopsis/summary of a Post Conference Perspectives involving Patrick Forde, MBBCh.

Forde discusses results from the LIBRETTO-431 trial (NCT04194944) of selpercatinib in RET fusion–positive (RET+) non–small cell lung cancer (NSCLC). RET fusions occur in about 1% of NSCLC, predominantly in nonsmokers with nonsquamous histology. Selpercatinib is approved in advanced RET fusion–positive NSCLC based on improved efficacy over multikinase inhibitors.

LIBRETTO-431 randomly assigned patients with previously untreated advanced RET fusion–positive NSCLC to platinum doublet chemotherapy plus pembrolizumab or selpercatinib. Selpercatinib significantly improved progression-free survival from 11.2 to 24.8 months, with an HR of 0.46 favoring selpercatinib. Response rates also improved by 18% with selpercatinib.

Forde states this confirmatory trial supports selpercatinib as the appropriate first-line therapy for RET fusion–positive advanced NSCLC. He notes some debate exists over whether such randomized trials are needed when targeted therapies show efficacy in single-arm trials but thinks this study confirms current practice. Confirmatory randomized trials with rare oncogenic drivers may not be possible or feasible to conduct, but this study provides definitive evidence to test for and treat RET fusion–positive disease with selpercatinib.

Video synopsis is AI-generated and reviewed by AJMC® editorial staff.