Selpercatinib in Early-Stage RET Fusion-Positive Non-Small-Cell Lung Cancer.
Summary
This phase 3 study, LIBRETTO-432, investigated the efficacy and safety of adjuvant selpercatinib in patients with early-stage (IB, II, or IIIA) RET fusion-positive non-small-cell lung cancer (NSCLC) after definitive therapy. Patients were randomized to receive selpercatinib or placebo for up to three years. The primary endpoint was event-free survival (EFS) in patients with stage II or IIIA disease. Results demonstrated a significant improvement in 2-year EFS with selpercatinib (92% vs 61% for stage II/IIIA, HR=0.17), with a similar trend across all stage IB-IIIA patients (94% vs 70%, HR=0.16). The safety profile was manageable, with elevated transaminases being the most common adverse events.
Analysis
This phase 3 study (LIBRETTO-432) provides high-level evidence (randomized, double-blind trial) for the use of adjuvant selpercatinib in patients with early-stage (II or IIIA) RET fusion-positive NSCLC. The dramatic improvement in event-free survival (HR of 0.17) indicates a major clinical benefit, positioning selpercatinib as a strong predictive biomarker for this population. These results justify a potential shift in clinical practice, integrating RET fusion screening and the use of adjuvant selpercatinib. Clinical impact could be observed within 1-3 years, pending regulatory approvals.