Multinational phase 3 trial of selpercatinib in early-stage RET fusion-positive non-small cell lung cancer

The RET inhibitor selpercatinib is approved for RET fusion-positive advanced or metastatic non-small cell lung cancer (NSCLC). The multinational phase 3 LIBRETTO-432 trial evaluated selpercatinib in early-stage NSCLC. Patients who had received definitive therapy with curative intents (surgery or radiotherapy with adjuvant systemic anticancer therapy, if applicable) were randomized 1:1 to receive adjuvant selpercatinib (n=75) or placebo (n=76) for up to 3 years.The primary endpoint was investigator-assessed event-free survival (EFS) in patients with stage II or IIIA disease (n=109). Two-year EFS rate among these patients was 92% with selpercatinib and 61% with placebo (HR 0.17; p<0.001). Among the 151 patients with stage IB, II, or IIIA disease, investigator-assessed EFS at 2 years was 94% with selpercatinib annd 70% with placebo (HR 0.17; p<0.001). The most common adverse events during the treatment period were increased levels of alanine aminotransferase and aspartate aminotransferase (grade ≥ 3 in 17% and 19%, respectively, in the selpercatinib group). Three deaths occurred, all in the placebo group, owing to disease progression. The authors conclude that among patients wirh stage II or IIIA RET fusion-positive NSCLC, EFS was significantly longer with adjuvant selpercatinib than with placebo.