A UCLA-led phase 3 trial is giving some early-stage lung cancer patients a far better shot at staying cancer-free. In people with resected RET fusion-positive non-small cell lung cancer, adjuvant selpercatinib (Retevmo) cut the risk of recurrence or death by 83% in a study presented at the American Society of Clinical Oncology and published in the New England Journal of Medicine.
Among patients with stage II to IIIA disease, 92% of those who received selpercatinib were alive without recurrence at two years, compared with 61% who received placebo.
What the trial showed
The LIBRETTO-432 trial enrolled 151 patients with early-stage RET fusion-positive non-small cell lung cancer. It randomized them 1:1 to receive selpercatinib or placebo after surgery or definitive radiotherapy, with investigator-assessed event-free survival as the primary endpoint, according to UCLA Health.
Eli Lilly reported that the study met that primary endpoint and confirmed the 83% reduction in the risk of recurrence or death with selpercatinib in the primary analysis.
What investigators said
“A targeted therapy drug can dramatically reduce that risk,” Jonathan Goldman, M.D., a lead investigator at UCLA, said during the ASCO plenary session and in the university's statement, according to UCLA Health. The results were presented during Sunday’s plenary session at the American Society of Clinical Oncology and will be published in the New England Journal of Medicine, the release noted.
Why RET testing matters
RET fusions are estimated to occur in roughly 1% to 2% of non-small cell lung cancers, which means only a small subset of patients would be eligible for this kind of adjuvant targeted treatment. Earlier work, including the registrational LIBRETTO-001 analysis, showed durable responses in advanced RET fusion-positive disease, as reported in the New England Journal of Medicine.
On the strength of those earlier data, selpercatinib is already approved for RET-altered tumors by the FDA. LIBRETTO-432 pushes that story earlier in the disease course, into the potentially curative, post-surgery window.
Safety and next steps
The safety profile in LIBRETTO-432 looked familiar to investigators. The most common grade 3 or higher side effects involved elevated liver enzymes, and those events were generally manageable with dose adjustments, according to Eli Lilly.
The company also reported that overall-survival data were immature at the time of the primary analysis and said it plans to submit the LIBRETTO-432 results to global health authorities.
What this could mean locally
At UCLA, clinicians say these data underline a very practical point: if you do not look for RET fusions up front, you will miss the patients who could benefit. They are calling for routine, comprehensive genomic testing at diagnosis so RET fusions can be identified before definitive therapy.
Experts previewing the ASCO meeting and analysts tracking the data told Targeted Oncology and Memorial Sloan Kettering that an adjuvant approval for selpercatinib could meaningfully change standard practice. The catch is that pathology labs, surgeons and insurers would all have to keep pace so the relatively small group of eligible patients can actually be found and treated.
For now, oncologists describe the LIBRETTO-432 results as a major advance, while still urging longer follow-up to confirm an overall-survival benefit. Independent reviewers and the study sponsor noted that overall-survival data were immature at the time of the primary analysis, according to CancerNetwork. Patients with lung cancer are being encouraged to talk with their care teams about genomic testing and whether trial enrollment or adjuvant targeted therapy is appropriate in their situation.
