Six years after hitting the market as the first targeted treatment for patients with a rare genetic tumor mutation, Eli Lilly’s Retevmo (selpercatinib) is solidifying its legacy with a new study that has shown “dramatic” outcomes and showcases the importance of RET fusion biomarker testing.
With several broad indications to its name, Retevmo has been targeting tumors with alterations in the rearranged during transfection (RET) gene for years now. However, the early-stage RET-fusion positive non-small cell lung cancer (NSCLC) patient population has yet to see major benefits from this push—until Lilly’s phase 3 Libretto-432.
Presented during the plenary session at the 2026 American Society of Clinical Oncology (ASCO) annual meeting in Chicago, Libretto-432 saw Retevmo able to reduce the risk of disease reoccurrence or death by a whopping 83% over placebo. The study was the first trial of its kind of weigh a selective RET kinase inhibitor as an adjuvant therapy in the patient population, Lilly pointed out in a May 31 press release, and took place among 151 patients who received treatment or placebo for up to three years after radiotherapy or surgery, with or without chemotherapy.
At 24 months in the primary analysis population of those with stage 2-3A disease, the event-free survival rate for Retevmo-treated patients was 92% compared to 61% in the placebo group.
For the wider overall study population of patients with stage 1B-3A disease, event-free survival rates came out to 94% in the treatment arm and 70% in the placebo group, Lilly reported.
Overall survival results, meanwhile, “trended in favor” of Retevmo but were immature at the time of analysis, according to the company.
Although RET fusions are more rare than other more commonly known cancer mutations such as EGFR and ALK, the results serve to establish RET fusions as a key biomarker to test for across all disease stages, the company said. RET fusions are seen in 1% to 2% of patients with NSCLC, study authors point out.
“Unlike EGFR and ALK, until now these patients have not had a way of addressing their disease when it occurs in the early-stage setting,” Lilly’s president of oncology and head of corporate business development, Jacob Van Naarden, explained in a recent interview with Fierce, noting that Libretto-432 “credentializes RET and selpercatinib in that same context.”
Two years after Retevmo’s market debut as a treatment for more advanced lung and thyroid cancers with a RET mutation, the drug snatched a much wider label to cover all locally advanced or metastatic solid tumors driven by the biomarker. Since then, it has become a dominant standard-of-care for the specific patient group, whose genomic alteration makes them “exquisitely sensitive” to the treatment, Van Naarden said.
To Lilly and Van Naarden, the “dramatic efficacy” seen across Retevmo’s studies reasserts the need for RET genomic tests during the early treatment process. While this testing is not exactly simple, the executive proposes that the extent of testing done for EGFR and ALK biomarkers, for example, should be commonplace for RET as well.
“There’s an underlying through line of biology here,” Van Naarden explained. “For lung cancer physicians and patients who have adopted EGFR and ALK directive therapies in early stage diagnosis,” RET is now also “firmly in the mix,” he emphasized.
Lilly plans to use the trial results as the basis for a proposed label expansion with global drug regulators “over the next couple months,” Van Naarden confirmed.
“This is in many ways the final chapter of the development program for this medicine,” the exec added, “but an exciting one, for sure.”
Given the rare nature of the biomarker, Retevmo isn’t much of a sales driver in Lilly’s oncology portfolio, generating sales of $364 million in 2024 and $456 million last year. The company essentially put all its RET chips in the drug after walking away from a next-generation RET inhibitor in 2024, which was meant to overcome acquired resistance to Retevmo. Both Retevmo and its scrapped successor came to Lilly from its $8 billion takeover of Loxo Oncology in 2019.