Clinical Summary:

• Design/Population: The phase 3 LIBRETTO-432 trial assessed adjuvant selpercatinib in patients with RET fusion-positive non-small cell lung cancer who underwent definitive locoregional therapy. 
• Key Outcomes: Selpercatinib significantly improved event-free survival compared with placebo with a safety profile that consistent with prior experience. 
• Clinical Relevance: Adjuvant selpercatinib may provide a new targeted treatment option for patients with early-stage RET fusion-positive non-small cell lung cancer.

Jonathan Goldman, MD, University of California, Los Angeles, California, discusses results from the phase 3 LIBRETTO-432 trial which evaluated adjuvant selpercatinib in patients with early-stage RET fusion-positive non-small cell lung cancer (NSCLC) who previously underwent definitive local therapy.

Results demonstrated that adjuvant selpercatinib significantly improved event-free survival compared with placebo following definitive treatment. In patients with stage II-IIIA disease, selpercatinib reduced the risk of recurrence or death by 83%, with a 2-year event-free survival rate of 91.5%. 

Dr Goldman presented these results during a plenary session at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois. 

Transcript:

Hello, my name is Dr. Jonathan Goldman. I'm a professor of medicine at UCLA, where I'm the director of clinical trials in thoracic oncology. It's very exciting for me to get the opportunity to present the results from our trial, LIBRETTO-432. This was an adjuvant trial evaluating the use of selpercatinib after definitive treatment—surgery mostly, but some got radiation—for stage 1B to 3A non-small cell lung cancer with a RET fusion. 

RET fusions are relatively rare, 1-2% of lung cancer, more often in younger patients and with little or no smoking history. But even though it's rare, it is quite important. And we found through the last years that identifying specific driving mutations in lung cancer and then using that information to select a treatment designed for that type of lung cancer really has dramatic benefits. 

Another recent revolution in lung cancer is moving these highly effective drugs from the metastatic setting to using them after surgery. We now have several trials showing us that doing that can really dramatically improve the disease-free or event-free survival. 

We have 2 other trials, the ADAURA and ALINA trials, that improved recurrence rates by more than 75%, or decreased recurrence rates by more than 75%. We wanted to see whether we could have the same type of benefit with an oral drug for a RET mutation, RET fusion. 

So, we screened almost 3 ½ thousand patients around the world and enrolled 151 patients. These all had a definitive treatment, surgery or radiation, and then they could, but they were not required to, have received adjuvant chemotherapy. Patients were then randomized one-to-one to either get selpercatinib or placebo for up to 3 years and then followed for event-free survival.

The primary endpoint was event-free survival in the stage 2 to 3A patients, and that's where we saw the hazard ratio of 0.17. One of the endpoints or data characteristics I like to consider is that at 2 years, the event-free survival was 92% in the patients on selpercatinib and only 61% for the patients on placebo. So, really a very dramatic and clear to understand benefit, I think, from the patient's standpoint. 

It was generally well tolerated. There were dose reductions, dose holds, but most of the adverse events were generally lower grade liver function test, blood test abnormalities. But I would consider in general this to be a well-tolerated drug.

In summary, I find this to be a practice-changing result. We've already used targeted therapies after surgery, and this is now the third target that I think is important in our adjuvant therapy. It provides us the opportunity to significantly delay cancer recurrence and hopefully to improve the cure rate.

Source:

Goldman JW, Yang X, Hochmair M, et al. Event-free survival with adjuvant selpercatinib in stage IB-IIIA RET fusion-positive NSCLC: Primary results of the phase 3 LIBRETTO-432 trial. Presented at the ASCO Annual Meeting. May 29 - June 2, 2026. Chicago, Illinois. LBA3.