Overview
- The LIBRETTO-432 randomized phase III trial, presented at the ASCO meeting in Chicago on Sunday, tested adjuvant selpercatinib versus placebo in 151 patients with resected or definitively treated stage IB–IIIA RET fusion–positive non-small cell lung cancer.
- In the primary analysis of 109 patients with stage II–IIIA disease, selpercatinib cut the risk of recurrence, progression, or death by about 83% (hazard ratio 0.17; P = .0003) and produced 2‑year event‑free survival rates of roughly 92% versus 61% for placebo.
- Safety matched the drug’s known profile in advanced disease, with reversible liver enzyme rises being common and dose modifications used to manage them; grade 3 or higher adverse events were more frequent on selpercatinib but were generally manageable.
- All three deaths observed in the trial occurred in the placebo arm, and selpercatinib reduced relapses across sites including the brain (1 CNS recurrence with selpercatinib versus 3 with placebo).
- Wider adoption will hinge on confirming overall survival with longer follow-up, accounting for placebo-to-drug crossover, and expanding routine molecular testing because RET fusions are rare and many early‑stage patients currently do not receive comprehensive NGS screening.