Eli Lilly and Company has announced positive topline results from the Phase III LIBRETTO-432 trial, demonstrating a statistically significant and clinically meaningful improvement in event-free survival (EFS) with Retevmo (selpercatinib) as adjuvant therapy in patients with stage II–IIIA RET fusion-positive non-small cell lung cancer (NSCLC).
The study met its primary endpoint, showing that adjuvant selpercatinib significantly reduced the risk of disease recurrence or death compared with placebo following definitive surgery or radiotherapy. While overall survival (OS) data remain immature due to a low number of events, results trended in favor of selpercatinib.
“We have consistently observed that cancer medicines can deliver their greatest impact when administered early in the course of a patient’s treatment journey. The LIBRETTO-432 results support this observation, demonstrating an effect size in line with the most striking data for targeted adjuvant therapy in lung cancer. Building on the adoption of targeted therapies for early-stage patients with EGFR- and ALK-driven lung cancer, we hope these results further accelerate the use of genomic testing for all people diagnosed with early-stage disease.”
said Jacob Van Naarden, executive vice president and president of Lilly Oncology
LIBRETTO-432 Trial
LIBRETTO-432 is a global, Phase III, randomized, double-blind, placebo-controlled trial evaluating adjuvant selpercatinib in patients with RET fusion–positive non-small cell lung cancer (NSCLC) following curative-intent surgery or radiotherapy, with or without prior adjuvant therapy.
A total of 151 patients were randomized 1:1 to receive
- selpercatinib or
- placebo.
The primary endpoint is investigator-assessed event-free survival (EFS) in patients with stage II–IIIA disease. Key secondary endpoints include overall survival, blinded independent central review (BICR)-assessed EFS, time to distant CNS recurrence, progression-free survival on subsequent therapy (PFS2), assay performance metrics for RET testing, and safety outcomes.
Safety Profile
The safety profile of selpercatinib in LIBRETTO-432 was generally consistent with prior studies. Known risks include hepatotoxicity, hypertension, QT prolongation, interstitial lung disease, hemorrhage, and hypersensitivity reactions. Liver enzyme elevations and hypertension remain among the most closely monitored toxicities in clinical practice.
No new safety signals were reported in this early-stage population.
Reinforcing the Role of Genomic Testing in Early Disease
Approximately 1–2% of NSCLC cases harbor RET fusions. With nearly half of NSCLC patients carrying actionable genomic alterations, the expanding use of molecular testing at diagnosis has become increasingly critical—not only in metastatic disease but now in early-stage settings.
The magnitude of EFS benefit observed in LIBRETTO-432 aligns with the transformative impact previously seen with EGFR- and ALK-targeted adjuvant therapies, underscoring the clinical value of identifying RET fusions early in the treatment journey.
About Selpercatinib
Selpercatinib (Retevmo) is a selective RET kinase inhibitor developed by Eli Lilly and Company for cancers driven by RET gene alterations, including RET fusion–positive non-small cell lung cancer (NSCLC) and RET-mutant thyroid cancers. First granted accelerated FDA approval in 2020, its indications have expanded to tumor-agnostic RET fusion–positive solid tumors and pediatric patients. The drug works by blocking abnormal RET signaling and has demonstrated strong systemic and intracranial activity.
Clinical evidence from the LIBRETTO-001 and LIBRETTO-531 trials showed high response rates, durable progression-free survival, and superiority over standard therapies in RET-driven cancers. Selpercatinib is taken orally twice daily and is generally well tolerated, with manageable side effects such as hypertension and elevated liver enzymes requiring routine monitoring.
Clinical Implications
The LIBRETTO-432 results position selpercatinib as a potential new standard of care for patients with resected stage II–IIIA RET fusion-positive NSCLC, pending full data presentation and regulatory review.
If approved in the adjuvant setting, selpercatinib would extend precision oncology deeper into early-stage lung cancer management, reinforcing the importance of comprehensive genomic profiling across all stages of disease.
Full results will be presented at an upcoming medical congress and submitted for peer-reviewed publication.