ASCO 2026 Plenary: LIBRETTO-432 — Adjuvant Selpercatinib Reduces Recurrence Risk by 83% in RET Fusion-Positive Early Lung Cancer (NEJM)

The Phase 3 LIBRETTO-432 trial, presented at the ASCO 2026 Plenary Session and simultaneously published in The New England Journal of Medicine, demonstrated that adjuvant selpercatinib (Retevmo; Eli Lilly) reduces the risk of disease recurrence or death by 83% in patients with RET fusion-positive early-stage non-small cell lung cancer following surgical resection. The trial enrolled 151 patients with resected Stage IB–IIIA RET fusion-positive NSCLC randomized to up to 3 years of selpercatinib (160 mg BID; n=75) vs. placebo (n=76). Median event-free survival was not reached for selpercatinib versus 31.8 months for placebo (HR 0.172, 95% CI 0.058–0.509; p=0.0003). Two-year EFS rates were 92% vs. 61%. RET fusions occur in approximately 1–2% of all NSCLC patients — roughly 2,000–3,000 patients per year in the US — and these patients previously received cytotoxic chemotherapy as adjuvant therapy with limited benefit. Selpercatinib is an oral once-daily selective RET inhibitor. This result establishes selpercatinib as the first approved adjuvant targeted therapy for RET fusion-positive NSCLC, with a magnitude of benefit (HR 0.172) comparable to osimertinib in EGFR-mutant NSCLC (ADAURA trial). The result continues a broader paradigm shift in early-stage NSCLC toward molecular subtype-specific targeted adjuvant strategies, moving the potentially curative phase of cancer care into the precision oncology era.