Our Take
Lilly has a clinical win in a tiny market, but the real bottleneck is whether hospitals will actually test for RET fusions in early-stage patients.
Why it matters
RET fusions affect only 1–2% of NSCLC patients, but Retevmo is the only approved TKI in the adjuvant space for this mutation. Expanding the label depends entirely on whether genetic testing becomes standard in early-stage lung cancer screening.
Do this week
Oncology networks: audit your stage IB–IIIA NSCLC testing protocols now to see whether RET fusion testing is included, so you can identify eligible patients before Retevmo label expansion hits.
Eli Lilly's RET inhibitor shows strong benefit in early-stage lung cancer
Eli Lilly presented Phase III LIBRETTO-432 results at ASCO 2026 for Retevmo (selpercatinib), a RET-targeting tyrosine kinase inhibitor, in early-stage (IB–IIIA) RET fusion-positive NSCLC patients in the adjuvant (post-surgery) setting. The trial enrolled 151 patients and randomized them 1:1 to three years of Retevmo or placebo following surgery.
Median event-free survival (EFS) was not reached in the Retevmo arm versus 31.8 months in the placebo arm (hazard ratio 0.172; p=0.0003). Two-year EFS was 91.5% for Retevmo compared to 61.1% for placebo. Three deaths occurred in the trial, all in the placebo arm from disease progression. (Company-reported.)
Toxicity was significant: 66.7% of Retevmo patients experienced grade 3 and above treatment-emergent adverse events compared to 23.7% on placebo. This toxicity burden led 17.3% of Retevmo patients to discontinue treatment, suggesting the dose or duration may require optimization.
Retevmo is currently approved for first-line metastatic RET-positive NSCLC and other RET-positive solid tumours. This adjuvant approval would expand its label into a new patient population at earlier disease stages.
The clinical win masks a diagnostic infrastructure problem
RET fusions are rare: they account for only 1–2% of all NSCLC patients and less than 1% in other solid tumours. Until now, the only adjuvant options for RET-positive early-stage NSCLC were immunotherapies like Keytruda (less effective in driver-mutation patients) or EGFR-targeting TKIs like Tagrisso (irrelevant for RET-positive disease).
Retevmo's main competitor, Gavreto (pralsetinib), has failed commercially and has no adjuvant trial underway, leaving Lilly alone in this niche. GlobalData projects Retevmo will earn $665 million in 2032 global sales from all indications combined (analyst estimate), so adjuvant expansion matters for revenue.
The real constraint is not efficacy—the trial shows that—but mutation testing frequency. RET fusion testing is not standard of care in early-stage NSCLC across most hospitals. Lilly's label expansion only benefits patients whose tumours are actually tested. Without a parallel shift in diagnostic ordering, the clinical win remains locked in the small subset of patients who happen to get tested today.
Test rates will determine commercial reality
Oncology practices and health systems need to review their early-stage NSCLC workflows now. Do you order RET fusion testing at diagnosis? Is it reflexive or opt-in? If adjuvant Retevmo becomes available, your ability to identify and enrol eligible patients depends on testing infrastructure you may not currently have.
The toxicity data also matters: one in six patients discontinued Retevmo due to adverse events. Practices should prepare for patient counselling on grade 3+ side effects and have dose-adjustment protocols ready before label expansion occurs.