Top Line: Does adjuvant selpercatinib improve outcomes for early stage, RET fusion positive NSCLC?
The Study: RET (REarranged during Transfection) encodes a transmembrane receptor tyrosine kinase. In about 1-2% of NSCLC, a chromosomal rearrangement fuses RET to an upstream partner gene that causes constitutive activation and downstream RAS-MAPK and PI3K-AKT signaling. Selpercatinib is a RET inhibitor that is approved for advanced RET-fusion positive NSCLC. In LIBRETTO-432, 151 patients who had received curative intent surgery or radiation for early stage NSCLC (72% were stage II-IIIA) were randomized to receive selpercatinib or placebo. The primary outcome of 2 year EFS was significantly higher in the overall cohort (94% v 70%) and among those with stage II-IIIA disease (92% v 61%). Most events happened in those with stage IIIA disease. Disease recurrence occurred in 7% who received selpercatinib and 35% who received placebo. The numbers were small, but brain recurrence was numerically less with CNS-active selpercatinib (1 event v 3 events).
TBL: Adjuvant selpercatinib significantly improved event free survival in patients RET fusion positive NSCLC treated with definitive surgery or radiation. | Wu, N Engl J Med 2026
The Study: RET (REarranged during Transfection) encodes a transmembrane receptor tyrosine kinase. In about 1-2% of NSCLC, a chromosomal rearrangement fuses RET to an upstream partner gene that causes constitutive activation and downstream RAS-MAPK and PI3K-AKT signaling. Selpercatinib is a RET inhibitor that is approved for advanced RET-fusion positive NSCLC. In LIBRETTO-432, 151 patients who had received curative intent surgery or radiation for early stage NSCLC (72% were stage II-IIIA) were randomized to receive selpercatinib or placebo. The primary outcome of 2 year EFS was significantly higher in the overall cohort (94% v 70%) and among those with stage II-IIIA disease (92% v 61%). Most events happened in those with stage IIIA disease. Disease recurrence occurred in 7% who received selpercatinib and 35% who received placebo. The numbers were small, but brain recurrence was numerically less with CNS-active selpercatinib (1 event v 3 events).
TBL: Adjuvant selpercatinib significantly improved event free survival in patients RET fusion positive NSCLC treated with definitive surgery or radiation. | Wu, N Engl J Med 2026