News|Articles|February 16, 2026

Adjuvant Selpercatinib Improves EFS in Early-Stage RET Fusion–Positive NSCLC

Fact checked by: Kyle Doherty , Kirsty Mackay

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Key Takeaways

Adjuvant selpercatinib improved investigator-assessed EFS versus placebo in stage II–IIIA RET fusion–positive NSCLC, establishing proof-of-concept for selective RET inhibition in the curative-intent setting.
Limited survival events precluded formal OS analysis, but the observed OS trend favored selpercatinib, with safety findings largely aligned with established toxicities.
The randomized, double-blind LIBRETTO-432 design enrolled stage IB–IIIA patients post-surgery or definitive radiotherapy, permitting adjuvant chemotherapy, and constrained time-to-randomization windows (10 or 26 weeks).
Eligibility required confirmed activating RET fusion and ECOG 0–1, while excluding other actionable drivers, prior RET inhibitors, post-definitive therapy recurrence, ILD/pneumonitis requiring steroids, and significant recent cardiovascular disease.
Secondary end points included BICR-assessed EFS, CNS distant recurrence timing, next-line PFS, and tolerability, complementing investigator-assessed EFS across primary and overall populations.

Improved EFS was seen when selpercatinib was administered as adjuvant therapy vs placebo in early-stage RET fusion–positive NSCLC.

Selpercatinib (Retevmo) led to a statistically significant and clinically meaningful improvement in investigator-assessed event-free survival (EFS) vs placebo as adjuvant therapy in the treatment of patients with early-stage RET fusion–positive non–small cell lung cancer (NSCLC), meeting the primary end point of the phase 3 LIBRETTO-432 trial (NCT04819100).¹

The limited number of survival events prevented formal assessment, but a trend toward improved overall survival (OS) was also observed with selpercatinib. The safety profile of selpercatinib in the trial was largely comparable to the established toxicity profile of the agent.

Detailed findings from the study will be shared at an upcoming medical congress, submitted to a peer-reviewed journal, and discussed with global regulatory agencies.

“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,” Jacob Van Naarden, executive vice president and president of Lilly Oncology, as well as the head of corporate business development at Eli Lilly and Company, stated in a news release. “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.”

Could LIBRETTO-432 Signal a New Adjuvant Frontier for RET+ Early-Stage NSCLC?

Selpercatinib delivered a statistically significant and clinically meaningful EFS benefit vs placebo in resected or definitively treated RET fusion–positive NSCLC, meeting the primary end point of the phase 3 LIBRETTO-432 trial.

Early OS signals are encouraging but immature, with too few survival events for formal analysis.

The study reinforces the momentum of biomarker-driven adjuvant lung cancer care, highlighting the growing need for routine genomic testing in early-stage disease alongside EGFR- and ALK-directed strategies.

What was LIBRETTO-432 designed to answer?

LIBRETTO-432 is a phase 3, global, multicenter, randomized, double-blind, controlled trial evaluating the efficacy and safety of selpercatinib vs placebo in patients with RET fusion–positive NSCLC following completion of definitive radiotherapy or surgery with curative intent, and other adjuvant therapy, if indicated.² The study is also the first randomized phase 3 trial to assess a selective RET kinase inhibitor in the adjuvant setting in this population.¹The agent is currently approved for use in 4 indications³:

Adult patients with locally advanced or metastatic NSCLC with a RET gene fusion, as detected by an FDA-approved test;
Adult and pediatric patients 2 years of age and older with advanced or metastatic medullary thyroid cancer with a RET mutation, as detected by an FDA-approved test, who require systemic therapy;
Adult and pediatric patients 2 years of age and older with advanced or metastatic thyroid cancer with a RET gene fusion, as detected by an FDA-approved test, who require systemic therapy and who are radioactive iodine-refractory; and
Adult and pediatric patients 2 years of age and older with locally advanced or metastatic solid tumors with a RET gene fusion, as detected by an FDA-approved test, that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options.

Who was eligible for the study?

To be eligible for LIBRETTO-432, patients must be at least 18 years old and have received a diagnosis of histologically confirmed stage IB, II, or IIIA NSCLC with an activating RET gene fusion in the tumor based on polymerase chain reaction, next-generation sequencing, or another approved molecule test.² Patients must also have received definitive locoregional therapy with curative intent and undergone or not been suitable for the available anticancer treatments.

In accordance with the study design, no more than 10 weeks was allowed between the completion of definitive therapy and randomization if no chemotherapy was given, and 26 weeks if adjuvant chemotherapy was administered. Adequate hematologic, hepatic, and renal function, and an ECOG performance status of 0 or 1 were also required.

If patients had additional oncogenic drivers, they would be excluded from enrollment. Additional exclusion criteria included prior treatment with a selective RET inhibitor, evidence of small cell lung cancer, clinical or radiologic evidence of disease recurrence or progression following definitive therapy, known or suspected interstitial lung disease or history of pneumonitis that required steroids, and clinically significant active cardiovascular disease or history of myocardial infarction within 6 months prior to the planned start of selpercatinib, among others.

A total of 151 patients were enrolled and randomly assigned 1:1 to receive adjuvant selpercatinib or placebo.

What are the key end points that will be evaluated?

The primary end point is investigator-assessed EFS in the primary analysis population, which included patients with stage II to IIIA RET fusion–positive NSCLC. Secondary end points include investigator-assessed EFS in the overall population, OS, blinded independent central review (BICR)–assessed EFS, time to distant disease recurrence in the central nervous system according to investigator and BICR, progression-free survival on the next line of treatment, and safety and tolerability.

References

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://investor.lilly.com/news-releases/news-release-details/lillys-retevmo-selpercatinib-delivers-substantial-event-free
A study of selpercatinib after surgery or radiation in participants with non-small cell lung cancer (NSCLC) (LIBRETTO-432). ClinicalTrials.gov. Updated March 4, 2026. https://clinicaltrials.gov/study/NCT04819100
Retevmo. Prescribing information. Eli Lilly and Company; 2024. Accessed February 16, 2026. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/213246s011s013lbl.pdf