Selpercatinib (RET inhibitor) slashes recurrence risk in resected RET fusion+ NSCLC (2-year EFS 92% vs 61%)

Selpercatinib is an oral, highly selective RET tyrosine kinase inhibitor (CNS-penetrant) tested as adjuvant targeted therapy in the Phase 3, double-blind LIBRETTO-432 trial (NCT04819100) in RET fusion–positive stage IB–IIIA NSCLC after definitive curative-intent therapy (surgery or radiotherapy ± adjuvant systemic therapy). In the primary stage II–IIIA population (n=109), 2-year investigator-assessed event-free survival (EFS) was 92% with selpercatinib vs 61% with placebo (HR 0.17, 95% CI 0.06–0.51; P<0.001); in the overall stage IB–IIIA population (n=151), 2-year EFS was 94% vs 70% (HR 0.17, 95% CI 0.06–0.49; P<0.001), with blinded independent central review consistent. Grade ≥3 ALT/AST elevations were notable (17%/19% with selpercatinib); three deaths occurred, all on placebo from progression—while adjuvant immunotherapy effects in unselected resected NSCLC are typically more modest (e.g., IMpower010 atezolizumab DFS HR ~0.66 in stage II–IIIA after chemo; KEYNOTE-091 pembrolizumab DFS HR ~0.72–0.76), a biomarker-matched TKI effect size here looks more “ADAURA-like” in magnitude (EGFR osimertinib DFS HR ~0.20).