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LB003/#1607  ENGOT-cx11/GOG-3047/KEYNOTE-A18: pembrolizumab or placebo with chemoradiotherapy for newly diagnosed, high-risk, locally advanced cervical cancer (LACC): results from interim analysis 2 for patients enrolled in Asia
  1. Yang Xiang1,
  2. Kosei Hasegawa2,
  3. Hong Zhu3,
  4. Qi Zhou4,
  5. Xiang Zhang5,
  6. Jung-Yun Lee6,
  7. Tomoka Usami7,
  8. Ekkasit Tharavichitkul8,
  9. Shiro Suzuki9,
  10. Ting-Chang Chang10,
  11. Guonan Zhang11,
  12. Chih-Long Chang12,
  13. Arb-Aroon Lertkhachonsuk13,
  14. Byoung-Gie Kim14,
  15. Kan Li15,
  16. Karin Yamada15,
  17. Sarper Toker15 and
  18. Domenica Lorusso16
  1. 1Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, National Clinical Research Center for Obstetric & Gynecologic Diseases, Beijing, China
  2. 2Saitama Medical University International Medical Center, Hidaka, Saitama, Japan
  3. 3Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, China
  4. 4Department of Gynecologic Oncology, Chongqing University Cancer Hospital, Chongqing, China
  5. 5Zhejiang Cancer Hospital, Hangzhou, China
  6. 6Severance Hospital, Yonsei University College of Medicine, Seoul, Korea, Republic of
  7. 7Department of Obstetrics and Gynecology, Ehime University Hospital, Ehime, Japan
  8. 8The Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, Chiang Mai University; Northern Thai Research Group of Radiation Oncology (NTRG-RO), Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
  9. 9Department of Gynecologic Oncology, Aichi Cancer Center Hospital, Nagoya, Japan
  10. 10Linkou Chang Gung Memorial Hospital, Taoyuan City, Taiwan (China)
  11. 11Gynecologic Oncology Center, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China
  12. 12Department of Obstetrics and Gynecology, MacKay Memorial Hospital, Taipei City, Taiwan (China)
  13. 13Department of Obstetrics and Gynaecology, Division of Gynaecologic Oncology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
  14. 14Division of Gynecologic Cancer, Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, Republic of
  15. 15Merck & Co., Inc., Rahway, United States of America
  16. 16Gynaecology Oncology Unit, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome, Italy and Humanitas San Pio X, Milan, Italy

Abstract

Introduction The phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 study (NCT04221945) evaluated pembrolizumab+concurrent chemoradiotherapy (CCRT) followed by pembrolizumab versus placebo+CCRT followed by placebo in patients with high-risk LACC. At interim analysis 1 (IA1), addition of pembrolizumab significantly improved PFS (HR, 0.70 [95% CI, 0.55–0.89]; P=0.0020) with a favorable trend for improved OS (HR, 0.73 [95% CI, 0.49–1.07]) in the intention-to-treat population. We present updated PFS and safety data from IA2 for patients enrolled in Asia.

Methods Patients had newly diagnosed, high-risk LACC (FIGO 2014 stage IB2-IIB with node-positive disease or stage III-IVA regardless of lymph node status). Patients were randomized (1:1) to receive 5 cycles of pembrolizumab 200mg or placebo Q3W plus CCRT, then 15 cycles of pembrolizumab 400mg or placebo Q6W. CCRT included 5 cycles (optional 6th dose) of cisplatin 40mg/m2 QW+EBRT, then brachytherapy. Primary endpoints were PFS per RECISTv1.1 by investigator assessment or histopathologic confirmation and OS.

Results 299 patients were enrolled in Asia (pembrolizumab+CCRT, n=153; placebo+CCRT, n=146). Median follow-up at database cutoff (January 8, 2024) was 31.2 (range, 12.8–43.0) months. Median PFS was not reached in either group; HR favored pembrolizumab+CCRT (0.61 [95% CI, 0.40–0.93]). 24-month PFS rate was 78.3% and 64.2% with pembrolizumab+CCRT and placebo+CCRT, respectively. No grade 5 treatment-related AEs occurred. Grade 3/4 treatment-related AE incidence was 78.9% and 78.1%, respectively. Immune-mediated AE incidence was 46.7% and 15.1% (grade 1/2, 42.1% and 13.7%).

Conclusion/Implications At IA2, pembrolizumab+CCRT continued to demonstrate PFS benefit versus placebo+CCRT, with manageable safety in patients with high-risk LACC enrolled in Asia.

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