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O008/#785 A multicenter, open-label, randomized, phase 3 study to compare the efficacy and safety of lenvatinib in combination with pembrolizumab vs treatment of physician’s choice in patients with advanced endometrial cancer: study 309/keynote-775
  1. V Makker1,
  2. N Colombo2,
  3. A Casado Herráez3,
  4. A Santin4,
  5. E Colomba5,
  6. D Miller6,
  7. K Fujiwara7,
  8. S Pignata8,
  9. S Baron-Hay9,
  10. I Ray-Coquard10,
  11. R Shapira11,
  12. K Ushijima12,
  13. J Sakata13,
  14. K Yonemori12,
  15. YM Kim14,
  16. EM Guerra15,
  17. UA Sanli16,
  18. M Mccormack17,
  19. J Huang18 and
  20. AD Smith19
  1. 1Memorial Sloan Kettering Cancer Center, Medicine, New York, USA
  2. 2University of Milan-Bicocca and European Institute of Oncology, Milan, Gynecologic Oncology, Milan, Italy
  3. 3San Carlos University Teaching Hospital, Department of Medical Oncology, Madrid, Spain
  4. 4Yale University School of Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, New Haven, USA
  5. 5Gustave Roussy Cancerology Institute, Department of Cancer Medicine, Villejuif, GINECO group, France
  6. 6University of Texas Southwestern Medical Center, Obstetrics and Gynecology, Dallas, USA
  7. 7Saitama Medical University International Medical Center, Department of Gynecologic Oncology, Hidaka, Japan
  8. 8Instituto Nazionale Tumori IRCCS Fondazione G Pascale, Department of Uro-gynaecological Oncology, Napoli, Italy
  9. 9Royal North Shore Hospital, Tba, St. Leonards, Australia
  10. 10University Claude Bernard Lyon I, Medical Oncology, Lyon, France
  11. 11Sheba Medical Center, Tba, TBA, Israel
  12. 12Kurume University School of Medicine, Department of Obstetrics and Gynecology, Kurume, Japan
  13. 13Aichi Cancer Center Hospital, TBA, Japan
  14. 14Asan Medical Center, University of Ulsan, Department of Obstetrics and Gynecology, Seoul, Korea, Republic of
  15. 15Hospital Universitario Ramón y Cajal, TBA, Madrid, Spain
  16. 16Ege University, TBA, Izmir, Turkey
  17. 1718University College London Hospitals NHS Foundation Trust, TBA, London, UK
  18. 18Eisai Inc, Woodcliff Lake, NJ, USA
  19. 19Eisai Ltd., TBA, Hatfield, UK


Objectives Results from a phase 1b/2 study showed lenvatinib (LEN) + pembrolizumab (pembro) has efficacy in patients (pts) with advanced endometrial carcinoma following prior treatment. Here, we describe the phase 3 study results of LEN + pembro vs treatment of physician’s choice (TPC) following platinum-based therapy in pts with advanced endometrial cancer (aEC).

Methods Pts were randomized (1:1) to receive LEN 20 mg orally QD + pembro 200 mg IV Q3W or TPC (doxorubicin at 60 mg/m2 IV Q3W or paclitaxel at 80 mg/m2 IV QW [3 weeks on; 1 week off]). Eligible pts had aEC with 1 prior platinum-based chemotherapy regimen or up to 2 prior platinum-based chemotherapy regimens, if 1 was given in the neoadjuvant/adjuvant setting. Randomization was stratified by DNA mismatch repair (MMR) status (centrally determined); pts with proficient (p)MMR tumors were further stratified by ECOG PS, geographic region, and prior history of pelvic radiation. Primary endpoints were PFS by blinded independent central review per RECIST v1.1 and OS. Key secondary endpoints included objective response rate (ORR) and safety. A graphical approach for multiplicity to control for type 1 error was used to test PFS for pts with pMMR aEC, then pts irrespective of MMR tumor status (i.e., all comers), followed SGO 2021 LEN 309 Abstract

Results 827 Pts (pMMR, n=697; dMMR, n=130) were randomized to receive LEN + pembro (n=411) or TPC (n=416). Median follow-up was 12.2 mo for pts randomized to LEN + pembro and 10.7 mo for pts randomized to TPC (data cutoff October 26, 2020). PFS was significantly improved with LEN + pembro vs TPC in pMMR aEC (median 6.6 vs 3.8 mo; HR 0.60) and in all-comers (median 7.2 vs 3.8 mo; HR 0.56). OS was significantly longer with LEN + pembro vs TPC in pMMR aEC (median 17.4 vs 12.0 mo; HR 0.68) and in all-comers (median 18.3 vs 11.4 mo; HR 0.62). ORR was significantly greater with LEN + pembro vs TPC in pMMR aEC (30.3% vs 15.1%) and in all-comers (31.9% vs 14.7%). Additional results are in the table. Median treatment duration was 231 days with LEN + pembro and 104.5 days with TPC. Overall, anygrade treatment-emergent adverse events (TEAEs) occurred at similar rates across treatment arms. Grade ≥3 TEAEs occurred in 89% of pts with LEN + pembro and 73% of pts with TPC. In the LEN + pembro arm, 30.8% pts discontinued LEN, 18.7% discontinued pembro, and 14.0% discontinued both study treatments due to a TEAE; the most common TEAEs were hypertension (64%), hypothyroidism (57%), diarrhea (54%) and nausea (50%).

Abstract O008/#785 Table 1

Conclusions LEN + pembro demonstrated statistically significant and clinically meaningful improvements in PFS, OS, and ORR vs TPC both in pts with aEC that was pMMR and in pts with aEC irrespective of MMR status. The safety profile of LEN + pembro was manageable and consistent with previously reported studies.

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