Lilly’s Retevmo cut the risk of disease recurrence or death by 83% as adjuvant therapy in people with early stage RET fusion positive lung cancer

The Phase 3 LIBRETTO-432 findings establish RET fusions, alongside EGFR mutations and ALK fusions, as biomarkers in early stage lung cancer that are linked to dramatic treatment outcomes, reinforcing the importance of comprehensive biomarker testing across every stage of disease. The data will be published in the New England Journal of Medicine and presented simultaneously during the Plenary Session at the 2026 ASCO Annual Meeting.

Eli Lilly and Company has shared findings from the Phase 3 LIBRETTO-432 clinical trial of Retevmo (selpercatinib) as adjuvant therapy versus placebo in patients with early stage (IB to IIIA) rearranged during transfection (RET) fusion positive non small cell lung cancer (NSCLC). The study hit its primary endpoint, producing a highly statistically significant and clinically meaningful improvement in investigator assessed event free survival (EFS), with selpercatinib reducing the risk of disease recurrence or death by 83% versus placebo in the primary analysis population.

The data will be published simultaneously in the New England Journal of Medicine and presented during the Plenary Session at the 2026 ASCO Annual Meeting taking place in Chicago, Illinois, as well as being featured in the meeting’s press programme.

“Patients with early-stage RET fusion-positive lung cancer face high recurrence risk, yet unlike those with EGFR or ALK alterations, have lacked a proven targeted treatment option,” said Jonathan Goldman, M.D., Professor of Medicine and Director of Clinical Trials at University of California, Los Angeles. “These LIBRETTO-432 results provide strong evidence that treating with selpercatinib after surgery or radiation can significantly lower that risk. The magnitude of benefit seen from adjuvant treatment with selpercatinib reinforces that comprehensive genomic testing at diagnosis is essential for all people with lung cancer and could lead to changes in clinical practice for treating early-stage RET-positive disease.”

LIBRETTO-432 is the first and only randomised Phase 3 study to assess the safety and efficacy of a selective RET kinase inhibitor as adjuvant therapy in this population. The trial enrolled 151 patients who were randomised 1:1 to receive either selpercatinib 160 mg twice daily or placebo for up to three years following definitive radiotherapy or curative intent surgery, with or without adjuvant chemotherapy.

At a median follow up of 24 months, investigator assessed event free survival in the primary analysis population (patients with stage II to IIIA disease, n=109) was significantly improved with selpercatinib compared with placebo (hazard ratio 0.17; 95% confidence interval 0.06 to 0.51; p<0.001). The event free survival rate at 24 months reached 92% (95% confidence interval 75.4 to 97.2) for selpercatinib, versus 61% (95% confidence interval 44.2 to 74.3) for placebo. Median event free survival had not been reached for selpercatinib, versus 31.8 months for placebo. In the overall study population (patients with stage IB to IIIA disease, n=151), event free survival results were consistent, also favouring selpercatinib (hazard ratio 0.17; 95% confidence interval 0.06 to 0.49; p<0.001). The event free survival rate at 24 months was 94% (95% confidence interval 81.5 to 98.0) in the selpercatinib group and 70% (95% confidence interval 55.5 to 80.1) in the placebo group. Findings were consistent across blinded independent central review and key subgroups, in both the primary analysis set and the overall study population. Overall survival results trended in favour of selpercatinib, but were immature at the time of this analysis with few events observed.

The overall safety profile of selpercatinib in LIBRETTO-432 was broadly consistent with previously reported trials across the selpercatinib development programme. The most common Grade 3 or higher adverse events were increased alanine aminotransferase (ALT), seen in 17% of the selpercatinib group versus 1% of the placebo group, and increased aspartate aminotransferase (AST), seen in 19% of the selpercatinib group versus 3% of the placebo group, both of which were manageable with dose modification.

“Selpercatinib has changed the treatment paradigm for patients with advanced RET-positive lung cancer, and now the substantial reduction in the risk of recurrence or death seen in LIBRETTO-432 highlights the potential for it to also become a new standard of care in the adjuvant setting for patients with early-stage RET-positive NSCLC,” said Jacob Van Naarden, executive vice president and president of Lilly Oncology. “These compelling results highlight the importance of bringing our effective medicines to patients early in their disease course when their impact can be greatest, and bring further urgency to the need for comprehensive biomarker testing for all lung cancers at diagnosis to enable effective therapy against EGFR, ALK and RET and for the development of medicines targeting emerging new biomarkers.”

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Related Topics and Keywords

Lilly's Retevmo, lung cancer, RET fusion-positive lung cancer, retevmo