Lenvatinib plus pembrolizumab versus chemotherapy as first-line therapy for advanced or recurrent endometrial cancer: Primary results of the phase III ENGOT-En9/LEAP-001 study.

Abstract

Objectives: Lenvatinib plus pembrolizumab led to significantly longer progression-free survival and overall survival than chemotherapy among patients with advanced endometrial cancer that has progressed following prior platinum-based chemotherapy in the randomized phase III study 309/KEYNOTE-775 trial. The randomized, open-label, phase III ENGOT-en9/LEAP-001 trial (NCT03884101) compares the efficacy and safety of lenvatinib plus pembrolizumab versus chemotherapy among patients with advanced or recurrent endometrial cancer who have received no prior chemotherapy or progressed >=6 months after neo/adjuvant chemotherapy. Method(s): From April 11, 2019, to March 25, 2021, 842 patients from 22 countries were enrolled. Patients with advanced (stage III-IV) or recurrent endometrial cancer with radiographically apparent disease not previously treated with chemotherapy (hormonal therapy and chemoradiation were allowed) or progressed >=6 months after neo/adjuvant chemotherapy were eligible. Patients were randomized 1:1 to receive pembrolizumab 200 mg every 3 weeks plus lenvatinib 20 mg daily or paclitaxel 175 mg/m2 every 3 weeks plus carboplatin AUC 6 every 3 weeks. Randomization was stratified based on proficient versus deficient mismatch repair (pMMR vs dMMR) status. The pMMR population (n = 642) was further stratified by prior adjuvant chemotherapy/chemoradiation (yes or no), measurable disease (yes or no), and ECOG performance status (0 or 1). Patients continued treatment for up to 35 cycles of pembrolizumab, 7 cycles of chemotherapy, or until disease progression, initiation of a new anticancer treatment, unacceptable toxicity, or withdrawal of consent. Dual primary study endpoints are progression-free survival (per RECIST version 1.1 by blinded independent central review) and overall survival in the pMMR and intention-to-treat groups. Secondary study endpoints include objective response rate, health-related quality of life, and safety and tolerability. The duration of response is an exploratory endpoint. Progression-free survival and overall survival for the 2 treatment arms will be compared using a stratified log-rank test. Result(s): TBD. Conclusion(s): Progression-free survival and overall survival data will be presented.Copyright © 2024