Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2023

Updated efficacy and safety of lenvatinib (LEN) + pembrolizumab (pembro) vs treatment of physician’s choice (TPC) in patients (pts) with advanced endometrial cancer (aEC): Study 309/KEYNOTE-775 (#196)

Vicky Makker 1 , Nicoletta Colombo 2 , Antonio Casado Herraez 3 , Bradley J. Monk 4 , Helen Mackay 5 , Alessandro D. Santin 6 , David S. Miller 7 , Richard Moore 8 , Sally Baron-Hay 9 , Isabelle Ray-Coquard 10 , Ronnie Shapira-Frommer 11 , Kimio Ushijima 12 , Kan Yonemori 13 , Yong Man Kim 14 , Eva M. Guerra Alia 15 , Ulus A. Sanli 16 , Jie Huang 17 , Jodi McKenzie 17 , Robert Orlowski 18 , Bas Ebaid 19 , Domenica Lorusso 20
  1. Memorial Sloan-Kettering Cancer Center, New York, NY, USA
  2. University of Milan-Bicocca, European Institute of Oncology IRCCS, Milan, Italy
  3. Hospital Clinico Universitario San Carlos, Madrid, Spain
  4. HonorHealth Research Institute, University of Arizona, Creighton University, Phoenix, AZ, USA
  5. Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Canada
  6. Yale University School of Medicine, New Haven, CT, USA
  7. University of Texas Southwestern Medical Center, Dallas, TX, USA
  8. University of Rochester Medical Center, Rochester, NY, USA
  9. Royal North Shore Hospital, St Leonards, NSW, Australia
  10. Centre Léon Bérard, University Claude Bernard, GINECO Group, Lyon, France
  11. Sheba Medical Center, Ramat, Israel
  12. Kurume University School of Medicine, Kurume, Japan
  13. National Cancer Center Hospital, Chuo-ku, Japan
  14. Asan Medical Center, University of Ulsan, Seoul, Republic of Korea
  15. Hospital Universitario Ramon y Cajal, Madrid, Spain
  16. Ege University, Izmir, Turkey
  17. Eisai Inc., Nutley, NJ, USA
  18. Merck & Co., Inc., Rahway, NJ, USA
  19. Eisai Australia Pty Ltd, Melbourne, Victoria, Australia
  20. Fondazione Policlinico Universitario Agostino Gemelli IRCCS and Catholic University of Sacred Heart, Rome, Italy

Aims

The ph3 Study 309/KEYNOTE-775 demonstrated statistically significant improvements in PFS, OS, and ORR with LEN+pembro vs TPC in pts with aEC.  We report updated Study 309/KEYNOTE-775 analyses.

Methods

Pts with aEC and 1 prior platinum-based chemotherapy regimen (up to 2 if 1 given in neoadjuvant/adjuvant setting) were randomized to LEN 20mg orally QD + pembro 200mg IV Q3W or TPC (doxorubicin 60mg/m2 IV Q3W or paclitaxel 80mg/m2 IV QW [3 wks on; 1 wk off]). Randomization was stratified by mismatch repair (MMR) status; pts with proficient (p)MMR tumors were further stratified by ECOG PS, geographic region, and pelvic irradiation. We report final pre-specified OS, PFS and ORR (BICR per RECIST v1.1), and safety (data cutoff: March 1, 2022). Analyses are descriptive.

Results

827 Pts (pMMR, n=697; deficient MMR, n=130) were randomized to LEN+pembro (n=411) or TPC (n=416). Median follow-up was 18.7mo (LEN+pembro) and 12.2mo (TPC). Median PFS (months) remained longer with LEN+pembro vs TPC in pMMR aEC (6.7 vs 3.8; HR, 0.60 [95% CI 0.50-0.72]) and in all-comers (7.3 vs 3.8; HR, 0.56 [95% CI 0.48-0.66]). Median OS (months) remained longer with LEN+pembro vs TPC in pMMR aEC (18.0 vs 12.2; HR, 0.70 [95% CI 0.58-0.83]) and in all-comers (18.7 vs 11.9; HR, 0.65 [95% CI 0.55-0.77]), despite some pts in the TPC arm receiving subsequent LEN+pembro (pMMR, 10.0%; all-comers; 8.7%). ORR (95% CI) for LEN+pembro vs TPC was 32.4% (27.5-37.6) vs 15.1% (11.5-19.3) in pMMR pts and 33.8% (29.3-38.6) vs 14.7% (11.4-18.4) in all-comers. 90% Of pts with LEN+pembro and 74% of pts with TPC had grade ≥3 TEAEs.

Conclusions

LEN+pembro continued to demonstrate improved efficacy vs TPC in pts with aEC who received prior platinum therapy. Safety was generally consistent with the primary analysis.

 

Previously presented at ESMO 2022, FPN: 525MO, V. Makker et al. Reused with permission.