Eli Lilly and Company has reported that its latest drug slashes lung cancer recurrence risk by 83% in landmark phase 3 trial.
The trial results are for the pharma powerhouse's RET-targeted therapy Retevmo (selpercatinib), showing a major reduction in the risk of cancer returning or death in patients with early-stage RET fusion-positive non-small cell lung cancer (NSCLC) after surgery or radiotherapy.
The LIBRETTO-432 trial met its primary endpoint, with selpercatinib cutting the risk of disease recurrence or death by 83% compared with placebo in the primary analysis population, a result described as both “highly statistically significant and clinically meaningful” in investigator-assessed event-free survival (EFS).
The findings position the drug as a potential new standard of care in the adjuvant setting, where treatment is given after curative surgery or radiation to prevent relapse. Unlike current targeted options for other lung cancer drivers such as EGFR or ALK, RET fusion-positive early-stage disease has had no established targeted therapy until now.
“These LIBRETTO-432 results provide strong evidence that treating with selpercatinib after surgery or radiation can significantly lower that risk.”
The study enrolled 151 patients with stage IB–IIIA disease, randomized evenly to receive either selpercatinib 160mg twice daily or placebo for up to three years. At a median follow-up of 24 months, the benefits were consistent and substantial across both the primary and overall study populations.
In stage II–IIIA patients, the hazard ratio for EFS was 0.17, with a 24-month EFS rate of 92% for selpercatinib versus 61% for placebo. Across all enrolled patients, the pattern held, with a hazard ratio of 0.17 and 24-month EFS rates of 94% versus 70%.
Median event-free survival was not reached in the treatment arm, compared with 31.8 months for placebo. Overall survival data were not yet mature, though early trends favored selpercatinib.
“Selpercatinib has changed the treatment paradigm for patients with advanced RET-positive lung cancer, and now the substantial reduction in the risk of recurrence or death seen in LIBRETTO-432 highlights the potential for it to also become a new standard of care in the adjuvant setting for patients with early-stage RET-positive NSCLC,” said Jacob Van Naarden, executive vice president and president of Lilly Oncology.
Safety findings were consistent with earlier studies of the drug. The most common severe side effects included elevated liver enzymes, with Grade 3 or higher ALT increases seen in 17% of patients on selpercatinib versus 1% on placebo, and AST increases in 19% versus 3%. These effects were described as manageable with dose adjustments.
