Retevmo lowers recurrence risk in early-stage RET-positive lung cancer

Even after surgery and other curative-intent treatment, many people with early-stage lung cancer face an unsettling reality: the cancer can come back. New findings suggest that a targeted therapy already used in advanced disease may help change that for a subset of patients.

Adjuvant Retevmo (selpercatinib) significantly reduced the risk of recurrence, progression or death in patients with early-stage RET fusion-positive non-small cell lung cancer (NSCLC), according to research published May 31, 2026, in The New England Journal of Medicine. The study was led by Yi-Long Wu, M.D., of the Guangdong Lung Cancer Institute in Guangzhou, China, and colleagues from the multinational LIBRETTO-432 trial.

RET fusions are uncommon genetic alterations found in about 1% to 2% of people with NSCLC. Although targeted therapies have improved outcomes in advanced RET-driven cancers, no targeted adjuvant therapy has previously been approved for early-stage RET fusion-positive disease. Patients with resectable NSCLC often undergo surgery, chemotherapy or other treatments with curative intent, yet recurrence remains common.

To evaluate whether Retevmo could reduce that risk, investigators enrolled 151 adults with Stage 1B, Stage 2 or Stage 3A RET fusion-positive NSCLC who had completed initial treatment, including surgery or radiotherapy followed by systemic therapy when appropriate. Participants were randomly assigned to take either Retevmo or placebo for up to three years.

Among 109 participants with Stage 2 or Stage 3A disease, 2-year event-free survival was 92% in the Retevmo group compared with 61% in the placebo group. The treatment reduced the risk of recurrence, progression or death by 83%. Disease recurrence occurred in just four people taking Retevmo versus 19 on placebo.

The benefit extended to the broader study population, which included patients with Stage 1B disease. In that analysis, 2-year event-free survival was 94% with Retevmo and 70% with placebo, corresponding to an 84% reduction in the risk of recurrence, progression or death. Independent central review produced similar findings.

Although overall survival data remain immature, all three deaths reported during the study occurred in the placebo group and were attributed to disease progression.

The safety profile was generally consistent with previous Retevmo studies. The most common serious toxicities (grade 3 or higher) were elevations in liver enzymes, which investigators said were generally manageable through monitoring and dose adjustments. Treatment discontinuation because of adverse events occurred in 17% of participants taking Retevmo and 1% of those on placebo.

According to the authors, the findings add further evidence that targeted therapies can improve outcomes in early-stage oncogene-driven lung cancers, similar to results previously seen with EGFR- and ALK-directed therapies. They noted several limitations, including the relatively small sample size necessitated by the rarity of RET fusions, limited representation of some racial and ethnic groups and the still-short follow-up period for assessing overall survival.

Even so, the researchers wrote that the results have the potential to change clinical practice in patients with early-stage disease.

In a news release issued by the study’s sponsor, Eli Lilly and Co., Jonathan Goldman, M.D., professor of medicine and director of clinical trials at the University of California, Los Angeles, and a study co-author, said patients with early-stage RET fusion-positive lung cancer have historically lacked a targeted adjuvant treatment option despite facing a high risk of recurrence.

“These LIBRETTO-432 results provide strong evidence that treating with selpercatinib after surgery or radiation can significantly lower that risk,” Goldman said in the news release. He added that the magnitude of benefit seen with adjuvant Retevmo reinforces the importance of comprehensive genomic testing at diagnosis for all patients with lung cancer and could lead to changes in the treatment of early-stage RET-positive disease.