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Introduction/Background Lenvatinib plus pembrolizumab is a standard of care for patients with advanced endometrial cancer (EC), following prior systemic therapy in any setting including neo/adjuvant. The randomized, open-label, phase 3 ENGOT-en9/LEAP-001 trial (NCT03884101) compares first-line lenvatinib plus pembrolizumab versus chemotherapy in patients with advanced/recurrent EC. Methodology Eligible patients had stage III-IV or recurrent, radiographically apparent, EC with no prior chemotherapy (hormonal therapy and chemoradiation permitted) or disease progression (PD) ≥6 months after neo/adjuvant chemotherapy. Patients were randomized 1:1 to lenvatinib 20 mg daily plus pembrolizumab 200 mg every 3 weeks (Q3W) or paclitaxel 175 mg/m2 Q3W plus carboplatin AUC 6 Q3W. Randomization was stratified by proficient versus deficient mismatch repair (MMR) status (pMMR versus dMMR), and in the pMMR stratum by prior adjuvant chemotherapy/chemoradiation (yes/no), measurable disease (yes/no), and ECOG performance status (0/1). Treatment continued for up to 35 cycles of pembrolizumab, 7 cycles of chemotherapy, or until PD/unacceptable toxicity. Dual primary endpoints were PFS (RECIST v1.1, blinded independent central review) and OS in the pMMR and intention-to-treat populations. Secondary endpoints included objective response rate and safety. Duration of response was an exploratory endpoint. Results Overall, 842 patients were randomized. At final analysis (data cutoff, October 2, 2023), after median follow-up of 38.4 (range, 30.3–52.9) months, OS was not statistically significant for non-inferiority of lenvatinib plus pembrolizumab versus chemotherapy in the pMMR population (HR, 1.02 95% CI, 0.83–1.26; non-inferiority P=0.2459875), thus no further statistical testing was performed (additional efficacy results in table 1). Treatment-related AEs occurred in 411/420 (97.9%) versus 398/411 (96.8%) treated patients in the lenvatinib plus pembrolizumab versus chemotherapy groups. Conclusion Lenvatinib plus pembrolizumab did not meet the prespecified statistical criterion for OS or PFS versus chemotherapy in patients with pMMR advanced/recurrent EC in the first-line setting. The safety profile was manageable and consistent with that established for the combination in EC. Disclosures Disclosures provided.
Marth et al. (Fri,) studied this question.