Adjuvant treatment with the targeted therapy drug selpercatinib can help reduce the risk that cancer will return, progress, or lead to death in patients with early-stage RET-positive non-small cell lung cancer (NSCLC).

The research was presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, which took place May 29 to June 2 in Chicago. 

“Despite receiving surgery or radiation followed by adjuvant chemotherapy or immunotherapy, up to two-thirds of patients with early-stage non-small cell lung cancer experience disease recurrence and may ultimately die from metastatic disease. No adjuvant targeted therapy has been approved for the subset of patients whose tumours harbour RET fusions, leaving an important gap in care for this population,” said lead study author Jonathan Goldman, MD, University of California, Los Angeles.

Selpercatinib is a type of targeted therapy drug that works by blocking the abnormal RET protein produced by RET fusion. It is already approved to treat people with advanced RET-positive NSCLC. In this study, researchers wanted to learn if it could also improve outcomes for people with earlier-stage disease. 

In the phase 3 LIBRETTO-432 clinical trial, participants who had stage IB to IIIA RET-positive NSCLC and had already received treatment were randomly assigned to receive either adjuvant selpercatinib (75 participants) or a placebo (76 participants) for up to 3 years after their main treatment.  

Key findings

The primary analysis was made up of 109 participants with stage II to IIIA disease. These participants had more advanced early-stage disease and a higher risk of recurrence. The median follow-up was 24 months for participants in the selpercatinib group and 27 months for participants in the placebo group. The planned 3-year follow-up period had not been reached at the time of this analysis, and the study is still ongoing.

• For the participants in the study who had stage II to IIIA disease, those receiving selpercatinib had significantly improved event-free survival (EFS). 
• For participants receiving selpercatinib, median EFS was not reached, which means more than half the participants were still alive and did not have the cancer come back or progress. 
• For those in the placebo group, the EFS was 31.8 months. 
• At 2 years, the EFS rate was 91.5% vs. 61.1% for people in the placebo group.
• Overall, selpercatinib reduced the risk of recurrence or death by about 83% compared to the placebo.
• When accounting for all participants in the study, EFS was not reached in either treatment group. 

The most common serious side effects in the selpercatinib group were increased alanine aminotransferase and increased aspartate aminotransferase levels, both of which can indicate liver damage.

Other common side effects of selpercatinib included dry mouth, diarrhea, and high blood pressure, most of which were mild and could be managed by adjusting the treatment dose. Overall, 3 study participants died from lung cancer, all of whom were in the placebo group.

“This is the first and only randomised phase 3 trial to evaluate a RET kinase inhibitor as adjuvant therapy in early-stage, RET-altered non-small cell lung cancer.

These compelling results establish a new standard of care for a rare subset of lung cancer and are immediately practice-changing. LIBRETTO-432 reinforces the need for comprehensive biomarker testing across all stages of non-small cell lung cancer,” said David R. Spigel, MD, FASCO, President and Chief Medical Officer at Sarah Cannon Research Institute and an ASCO Expert in lung cancer.

The researchers plan to perform a longer follow-up to reach a more mature assessment of secondary outcomes, including overall survival; to provide additional insights across subgroups, such as patients with stage IB disease; and to further strengthen the overall dataset.

Watch the related interview here.

Source: ASCO