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- In the Phase 3 LIBRETTO-431 study, Retevmo more than doubled progression-free survival (PFS) compared to chemotherapy plus pembrolizumab in patients with advanced or metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC)
- In the Phase 3 LIBRETTO-531 study, Retevmo provided a 72% improvement in PFS compared to cabozantinib or vandetanib in patients with advanced or metastatic RET-mutant medullary thyroid cancer (MTC)
INDIANAPOLIS, Oct. 21, 2023 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) today announced results from both the LIBRETTO-431 Phase 3 study, which evaluated Retevmo® (selpercatinib) versus platinum-based chemotherapy — with or without pembrolizumab — as an initial treatment for patients with advanced or metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC), and the LIBRETTO-531 Phase 3 study, which evaluated Retevmo versus multikinase inhibitors (MKIs) in patients with advanced or metastatic RET-mutant medullary thyroid cancer (MTC). In both clinical studies, results were based on pre-specified interim efficacy analyses conducted by independent data monitoring committees (IDMC). Results from the LIBRETTO-431 and LIBRETTO-531 Phase 3 trials were presented in a Presidential Symposium at the European Society for Medical Oncology (ESMO) Congress 2023 and simultaneously published in the New England Journal of Medicine.
"These results from LIBRETTO-431 and LIBRETTO-531 are striking and provide critical evidence supporting the importance of optimizing initial therapy for patients with RET-driven cancers," said David Hyman, M.D., chief medical officer, Lilly. "We are excited to be sharing these data with the clinical community in both NEJM and at ESMO. It is our hope that these data lead to further adoption of biomarker testing in the initial treatment journey for people with NSCLC and MTC and help make Retevmo a standard initial treatment option for all appropriate patients."
The labeling for Retevmo contains warnings and precautions for hepatotoxicity (evidence of liver dysfunction), interstitial lung disease (ILD)/pneumonitis, hypertension, QT interval prolongation, hemorrhagic events, hypersensitivity, tumor lysis syndrome, risk of impaired wound healing, hypothyroidism, and embryo-fetal toxicity.
RETFusion-Positive NSCLC: Data from LIBRETTO-431LIBRETTO-431 is a Phase 3, randomized, open-label trial that evaluated Retevmo in patients with advanced or metastatic, treatment-naïve RET fusion-positive NSCLC. In the study, patients were randomly assigned to receive Retevmo, or pemetrexed and the investigator's choice of platinum-based chemotherapy (cisplatin or carboplatin) with or without pembrolizumab — which is a current first-line standard of care treatment option. LIBRETTO-431 is the first randomized trial that compared the safety and effectiveness of a targeted therapy to a PD-1 inhibitor plus chemotherapy in a biomarker-selected NSCLC patient population. The primary endpoint was tested first in patients stratified by intent-to-treat (ITT) with pembrolizumab if assigned to the control arm (ITT-pembrolizumab), then tested in the ITT population if deemed positive.
"These data provide clear evidence that Retevmo offers highly meaningful clinical impact for patients diagnosed with RET fusion-positive NSCLC and it should be considered as the first treatment option for these patients," said Caicun Zhou, M.D., Ph.D., director and professor at the Cancer Institute of Tongji University School of Medicine and Shanghai Pulmonary Hospital, and LIBRETTO-431 primary investigator. "While there is often urgency to treat, these results further highlight the importance of incorporating routine biomarker testing into a patient's care plan to direct early clinical decision-making towards the most effective therapies."
A total of 256 patients received at least one dose of study treatment (Retevmo, 158; control arm, 98). Of the 261 patients in the ITT population, 159 were randomly assigned to Retevmo and 102 to the control arm. Of the 212 patients in the ITT-pembrolizumab population, 129 were randomly assigned to Retevmo and 83 to pembrolizumab with chemotherapy. Patients randomized to the control arm who had disease progression confirmed by blinded independent central review (BICR) were eligible for optional crossover to Retevmo.
In the ITT-pembrolizumab population, the median PFS by BICR was 24.8 months (95% CI: 16.9, not estimable [NE]) with Retevmo versus 11.2 months (95% CI: 8.8, 16.8) in the control arm, corresponding to a hazard ratio (HR) of 0.465 (95% CI: 0.309, 0.699; p
