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#88 Lenvatinib plus pembrolizumab versus chemotherapy as first-line therapy for advanced or recurrent endometrial cancer: primary results of the phase 3 ENGOT-en9/LEAP-001 study
  1. Christian Marth1,
  2. Richard G Moore2,
  3. Mariusz Bidzinski3,
  4. Sandro Pignata4,
  5. Ali Ayhan5,
  6. M Jesús Rubio6,
  7. Mario Beiner7,
  8. Marcia Hall8,
  9. Christof Vulsteke9,
  10. Elena Ioana Braicu10,11,
  11. Kenzo Sonoda12,
  12. Xiaohua Wu13,
  13. Sophia Frentzas14,
  14. André Mattar15,
  15. Jodi McKenzie16,
  16. Lili Yao17,
  17. Vivek Khemka17,
  18. Lucy Gilbert18 and
  19. Vicky Makker19
  1. 1AGO-Austria and Department of Obstetrics and Gynecology, Medical University of Innsbruck, Innsbruck, Austria
  2. 2Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Wilmot Cancer Institute, University of Rochester, Rochester, New York, USA
  3. 3Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie, Warsaw, Poland
  4. 4Department of Urology and Gynecology, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Napoli, Italy
  5. 5Turkish Society of Gynecologic Oncology (TRSGO), Baskent University, Ankara, Turkey
  6. 6H. Reina Sofía de Córdoba and GEICO Group, Córdoba, Spain
  7. 7Meir Medical Center, Kfar Saba, Israel
  8. 8Mount Vernon Cancer Centre, Northwood, UK
  9. 9Integrated Cancer Center Ghent, Department of Medical Oncology, AZ Maria Middelares Ghent and Center of Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp, Wilrijk, Antwerp, Belgium
  10. 10Charité Universitätsmedizin Berlin and North Eastern German Society for Gynecologic Oncology (NOGGO), Berlin, Germany
  11. 11Department of Obstetrics and Gynecology, Stanford University, Stanford, USA
  12. 12Gynecology Service, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan
  13. 13Fudan University Shanghai Cancer Center, Shanghai, China
  14. 14Department of Medical Oncology, Monash Health and Monash University, Melbourne, Australia
  15. 15Hospital da Mulher, São Paulo, Brazil
  16. 16Eisai Inc., Nutley, New Jersey, USA
  17. 17Merck and Co., Inc., Rahway, New Jersey, USA
  18. 18Division of Gynecologic Oncology, McGill University Health Centre, Montreal, Quebec, Canada
  19. 19Memorial Sloan Kettering Cancer Center, New York, New York, USA


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.

Abstract #88 Table 1

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