Adjuvant treatment with the selective RET inhibitor selpercatinib significantly reduced the risk of disease recurrence, progression, or death among patients with resected stage IB to IIIA RET fusion–positive non–small cell lung cancer (NSCLC), according to results from the phase III LIBRETTO-432 trial presented at the 2026 ASCO Annual Meeting (Abstract LBA3).
RET fusions occur in approximately 1% to 2% of patients with NSCLC. Although selpercatinib is already approved for advanced RET-positive NSCLC, no targeted adjuvant therapy has previously been available for patients with early-stage disease who remain at high risk for recurrence following definitive treatment.
“Despite receiving surgery or radiation followed by adjuvant chemotherapy or immunotherapy, up to two-thirds of patients with early-stage [NSCLC] experience disease recurrence and may ultimately die from metastatic disease,” said lead study author Jonathan Goldman, MD, of the University of California, Los Angeles. “No adjuvant targeted therapy has been approved for the subset of patients whose tumors harbor RET fusions, leaving an important gap in care for this population.”
Study Details
The global, randomized, placebo-controlled phase III LIBRETTO-432 trial enrolled 151 patients from 22 countries with stage IB to IIIA RET fusion–positive NSCLC who had completed definitive therapy. Participants were randomly assigned to receive either adjuvant selpercatinib (n = 75) or placebo (n = 76) for up to 3 years after their main treatment.
Key Results
The primary efficacy analysis focused on 109 patients with stage II to IIIA disease, a subgroup considered at higher risk for recurrence. At a median follow-up of 24 months in the selpercatinib arm and 27 months in the placebo arm, treatment with selpercatinib resulted in a substantial improvement in event-free survival, the study’s primary endpoint.
Median event-free survival was not reached in the selpercatinib group, indicating that more than half of treated patients remained alive without recurrence or disease progression at the time of analysis. In contrast, median event-free survival was 31.8 months in the placebo group. At 2 years, the event-free survival rate was 91.5% with selpercatinib compared with 61.1% with placebo.
Overall, adjuvant selpercatinib reduced the risk of recurrence or death by approximately 83% compared with placebo. Among all 151 enrolled patients, the error-controlled event-free survival hazard ratio was 0.165 (95% confidence interval = 0.056–0.485, P = .0002), and median event-free survival was not reached in either treatment arm.
The most common serious adverse events in the selpercatinib group were elevations in alanine aminotransferase and aspartate aminotransferase, possibly indicating liver injury. Other frequently reported adverse effects included dry mouth, diarrhea, and hypertension, most of which were mild and manageable with dose modifications. Three deaths from lung cancer occurred during the study, all in the placebo arm.
The trial remains ongoing, and investigators plan a longer follow-up to assess secondary endpoints, including overall survival, and to better understand outcomes in specific patient subgroups, including those with stage IB disease.
DISCLOSURE: For full disclosures of the study authors, visit coi.asco.org.
