PURPOSE: Lenvatinib plus pembrolizumab (len + pembro) significantly improved progression-free survival (PFS) and overall survival (OS) versus chemotherapy in previously treated advanced or recurrent endometrial cancer (aEC) in the phase III Study 309/KEYNOTE-775. We report results from the phase III, randomized, open-label European Network of Gynaecological Oncological Trial-en9/LEAP-001 study (ClinicalTrials.gov identifier: NCT03884101) that evaluated len + pembro versus chemotherapy in first-line aEC. METHODS: Patients with stage III to IV or recurrent, radiographically apparent EC and no previous chemotherapy or disease progression ≥6 months after neo/adjuvant platinum-based chemotherapy were randomly assigned 1:1 to lenvatinib 20 mg once daily plus pembrolizumab 200 mg once every 3 weeks or paclitaxel 175 mg/m RESULTS: Eight hundred forty-two patients were randomly assigned (len + pembro, n = 420 [pMMR population, n = 320]
chemotherapy, n = 422 [pMMR population, n = 322]). At FA (data cutoff, October 2, 2023), median PFS (95% CI) in the pMMR population was 9.6 (8.2 to 11.9) versus 10.2 (8.4 to 10.5) months with len + pembro versus chemotherapy (hazard ratio [HR], 0.99 [95% CI, 0.82 to 1.21]) and among all-comers was 12.5 (10.3 to 15.1) versus 10.2 (8.4 to 10.4) months (HR, 0.91 [95% CI, 0.76 to 1.09]
descriptive analyses). Median OS (95% CI) in the pMMR population was 30.9 (25.4 to 37.7) versus 29.4 (26.2 to 35.4) months with len + pembro versus chemotherapy (HR, 1.02 [95% CI, 0.83 to 1.26]
noninferiority CONCLUSION: First-line len + pembro did not meet prespecified statistical criteria for PFS or OS versus chemotherapy in pMMR aEC.