Selpercatinib is a highly selective, potent, and brain-penetrant RET inhibitor approved for patients with RET fusion-positive advanced or metastatic non-small cell lung cancer (NSCLC). However, RET-directed therapy has not previously demonstrated benefit in patients with stage IB-IIIA RET-positive NSCLC, where recurrence rates remain high after definitive treatment and no adjuvant targeted therapy is currently approved. The phase 3 LIBRETTO-432 trial (NCT04819100) provides the first randomized evidence supporting a targeted adjuvant therapy approach for patients with resected RET fusion–positive NSCLC.
In this global, placebo-controlled study, patients with stage IB to IIIA disease who had completed definitive local therapy were randomized to receive selpercatinib or placebo for up to 3 years. At a median follow-up of approximately 4 years, adjuvant selpercatinib significantly improved event-free survival (EFS), the study’s primary endpoint.
Among patients with stage II to IIIA disease, selpercatinib reduced the risk of recurrence or death by 83% compared with placebo (hazard ratio [HR], 0.17). Median event-free survival (EFS) was not reached with selpercatinib versus 31.8 months with placebo, and the 24-month EFS rate was 92% versus 61%, respectively. Overall survival data remain immature at this time.
Similar benefit was observed across the overall stage IB to IIIA population, with an EFS HR of 0.17 and 24-month EFS rates of 94% with selpercatinib and 70% with placebo.
For multidisciplinary oncology teams, these findings underscore the importance of comprehensive biomarker testing at diagnosis, as identification of RET fusions may now influence treatment decisions in both advanced- and early-stage disease.
The safety profile was generally consistent with prior experience with selpercatinib. The most common grade 3 or higher adverse events included elevations in alanine aminotransferase and aspartate aminotransferase levels. No new safety signals were identified.
Overall, LIBRETTO-432 provides compelling evidence supporting adjuvant selpercatinib for patients with resected RET fusion-positive NSCLC and represents a significant advance in extending precision oncology strategies into earlier stages of lung cancer care.
Source: Goldman JW, Yang X, Hochmair M, et al. Event-free survival with adjuvant selpercatinib in stage IB-IIIA RET fusion-positive NSCLC: primary results of the phase 3 LIBRETTO-432 trial. Presented at: ASCO Annual Meeting. May 29-June 2, 2026; Chicago, IL. Abstract LBA3.