Adjuvant Selpercatinib Improves EFS in Early-Stage RET+ NSCLC

Adjuvant therapy with selpercatinib (Retevmo) demonstrated a clinically meaningful and statistically significant event-free survival (EFS) improvement vs placebo among patients with early-stage RET fusion-positive non–small cell lung cancer (NSCLC), according to a press release on topline findings from the phase 3 LIBRETTO-432 trial (NCT04819100).¹

The EFS improvement with selpercatinib reached the trial’s primary end point. Although overall survival (OS) data were immature at the time of analysis, results trended in favor of the selpercatinib arm. Additionally, the safety profile of selpercatinib in the LIBRETTO-432 trial was comparable with previous reports of the agent.

Investigators plan to present detailed findings from the LIBRETTO-432 trial at a future medical meeting. They also look to submit these data to a peer-reviewed journal and discuss their findings with regulatory health authorities around the world.

“We have consistently observed that cancer medicines can deliver their greatest impact when administered early [during] 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,” Jacob Van Naarden, executive vice president and president of Lilly Oncology, the developer of selpercatinib, stated in the press release.¹ “Building on the adoption of targeted therapies for patients with early-stage 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.”

Developers designed selpercatinib as a highly select and potent inhibitor of the RET kinase that harbors central nervous system (CNS) activity. The agent is an FDA-approved oral therapy recommended for dosing at 120 mg or 160 mg depending on the patient’s weight, with treatment occurring twice daily until progressive disease or unacceptable toxicity.

Investigators of the international, multicenter, double-blind phase 3 LIBRETTO-432 study are evaluating selpercatinib vs placebo among patients with RET fusion-positive NSCLC who have completed prior definitive radiotherapy or surgery and other adjuvant treatment, if applicable. A total of 151 patients were randomly assigned 1:1 to receive selpercatinib or matched placebo in the adjuvant setting.

The trial’s primary end point was EFS per investigator evaluation, defined as the time from random assignment to disease recurrence or progression or death from any cause.² Secondary end points included OS, time to distant disease recurrence in the CNS, progression-free survival on the next line of therapy, mean change from baseline in NSCLC symptoms based on the 7-item NSCLC Symptom Assessment Questionnaire, and mean change from baseline for physical function based on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30.

Patients 18 years and older with histologically confirmed stage IB, II, or IIIA NSCLC; an activating RET gene fusion per polymerase chain reaction, next-generation sequencing, or other molecular tests; prior definitive locoregional with curative intent; and an ECOG performance status of 0 or 1 were eligible for enrollment on the trial. Having adequate hematologic, hepatic, and renal function was another requirement for study entry.

Those with known additional oncogenic drivers in NSCLC, evidence of small cell lung cancer, clinical or radiologic evidence of disease recurrence or progression after definitive treatment, or known or suspected interstitial fibrosis or interstitial lung disease were ineligible for study entry. Patients were also unable to enroll if they had clinically significant active cardiovascular disease or history of myocardial infarction within 6 months of beginning study treatment; known active hepatitis B or C; or active uncontrolled systemic bacterial, viral, or fungal infections or serious ongoing intercurrent illness.

References

1. Lilly's Retevmo (selpercatinib) delivers substantial event-free survival benefit as an adjuvant therapy in early-stage RET fusion-positive lung cancer. News release. Eli Lilly and Company. February 16, 2026. Accessed February 16, 2026. https://tinyurl.com/3pwdvr99
2. A study of selpercatinib after surgery or radiation in participants with non-small cell lung cancer (NSCLC) (LIBRETTO-432). ClinicalTrials.gov. Updated February 9, 2026. Accessed February 16, 2026. https://tinyurl.com/3tp4xpb4