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161 Pembrolizumab plus chemoradiotherapy for high-risk locally advanced cervical cancer: the randomized, double-blind, phase 3 ENGOT-Cx11/GOG-3047/KEYNOTE-A18 study
  1. Domenica Lorusso1,
  2. Yang Xiang2,
  3. Kosei Hasegawa3,
  4. Giovanni Scambia4,
  5. Manuel Leiva5,
  6. Pier Ramos-Elias6,
  7. Alejandro Acevedo7,
  8. Julia Vizkeleti8,
  9. Andrea Gomes9,
  10. Fernando Contreras Mejía10,
  11. Ari Reiss11,
  12. Ali Ayhan12,
  13. Jung-Yun Lee13,
  14. Valeriya Saevets14,
  15. Flora Zagouri15,
  16. Kan Li16,
  17. Karin Yamada16,
  18. Sarper Toker16,
  19. Sandro Pignata17 and
  20. Linda R Duska18
  1. 1Gynaecology Oncology Unit, Fondazione Policlinico Universitario A Gemelli IRCCS and Catholic University of Sacred Heart, Rome, Italy
  2. 2Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, National Clinical Research Center for Obstetric and Gynecologic Diseases, Beijing, China
  3. 3Saitama Medical University International Medical Center, Hidaka, Saitama, Japan
  4. 4Scientific Directorate, Fondazione Policlinico Universitario Agostino Gemelli IRCCS and Catholic University of the Sacred Heart, Rome, Italy
  5. 5Instituto de Oncologia y Radioterapia Clinica Ricardo Palma, Lima, Peru
  6. 6Integra Cancer Institute, Edificio Integra Medical Center, Guatemala City, Guatemala
  7. 7Oncocentro, Valparaiso, Chile
  8. 8National Institute of Oncology, Centre of Radiotherapy, Budapest, Hungary
  9. 9Liga Norte Riograndense Contra o Cancer, Rio Grande Do Norte, Brazil
  10. 10Instituto Nacional de Cancerologia, Bogota, Colombia
  11. 11Rambam Medical Center, Gyneco-oncology Unit, Haifa, Israel
  12. 12Turkish Society of Gynecologic Oncology (TRSGO), Baskent University, Ankara, Turkey
  13. 13Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
  14. 14Chelyabinsk Regional Clinical Center Oncology and Nuclear Medicine, Chelyabinsk, Russia
  15. 15Alexandra Hospital, Athens, Greece
  16. 16Merck and Co., Inc., Rahway, Nj, USA
  17. 17Department of Urology and Gynecology, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Napoli, Italy
  18. 18University of Virginia School of Medicine, Charlottesville, Va, USA

Abstract

Introduction/Background Pembrolizumab has shown efficacy in patients with cervical cancer. The effect of chemoradiotherapy may be enhanced by immunotherapy. ENGOT-cx11/GOG-3047/KEYNOTE-A18 (NCT04221945) assessed efficacy and safety of pembrolizumab + concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer (LACC).

Methodology Eligible patients with newly diagnosed, previously untreated, high-risk LACC (FIGO 2014 stage IB2-IIB with node-positive disease or stage III-IVA) were randomized 1:1 to receive 5 cycles of pembrolizumab 200 mg or placebo Q3W + CCRT, then 15 cycles of pembrolizumab 400 mg or placebo Q6W. The CCRT regimen included 5 cycles (with optional sixth dose) of cisplatin 40 mg/m2 Q1W + EBRT then brachytherapy. Patients were stratified by planned EBRT type (IMRT/VMAT vs non-IMRT/non-VMAT), stage at screening (stage IB2-IIB vs III-IVA) and planned total radiotherapy dose. Primary endpoints were PFS per RECIST v1.1 by investigator and OS.

Results 1060 patients were randomized to pembrolizumab+CCRT (n=529) or placebo+CCRT (n=531). At the protocol-specified first interim analysis (January 9, 2023, data cutoff), median follow-up was 17.9 mo (range, 0.9–31.0). Pembrolizumab+CCRT showed a statistically significant improvement in PFS vs placebo+CCRT. 24-mo PFS was 67.8% with pembrolizumab+CCRT vs 57.3% with placebo+CCRT; median PFS was not reached in either group (HR=0.70 [95% CI, 0.55–0.89; P=0.0020]); results were consistent across all prespecified subgroups. With only 103 events (42.9% maturity), the addition of pembrolizumab to CCRT showed a favorable trend in OS (HR=0.73 [95% CI, 0.49–1.07]); these data have not crossed the boundary of statistical significance. Grade ≥3 TRAE incidence was 67.0% in the pembrolizumab+CCRT group and 60.0% in the placebo+CCRT group.

Conclusion Pembrolizumab+CCRT showed a statistically significant and clinically meaningful improvement in PFS and a favorable trend in OS compared with placebo+CCRT in patients with high-risk locally advanced cervical cancer and had a manageable safety profile. These data suggest pembrolizumab+CCRT can be considered as a new standard of care for this population.

Disclosures Disclosures are provided via the ESGO COI Disclosure forms.

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