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58 KEYNOTE-826: Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for persistent, recurrent, or metastatic cervical cancer
  1. N Colombo1,
  2. C Dubot2,
  3. D Lorusso3,
  4. V Caceres4,
  5. K Hasegawa5,
  6. R Shapira-Frommer6,
  7. K Tewari7,
  8. P Salman8,
  9. E Hoyos Usta9,
  10. E Yañez10,
  11. M Gümüş11,
  12. M Olivera Hurtado de Mendoza12,
  13. V Samouëlian13,
  14. V Castonguay14,
  15. A Arkhipov15,
  16. S Toker16,
  17. K LI16,
  18. S Keefe16 and
  19. B Monk17
  1. 1University of Milan-Bicocca and European Institute of Oncology (IEO) IRCCS, Milan, Italy
  2. 2Institut Curie Saint-Cloud, Group d’Investigateurs Nationaux pour l’Etude des Cancers Ovariens (GINECO), Saint-Cloud, France
  3. 3Fondazione Policlinico Universitario A Gemelli IRCCS and Catholic University of Sacred Heart, Rome, Italy
  4. 4Institute of Oncology Angel H. Roffo, Buenos Aires , Argentina
  5. 5Saitama Medical University International Medical Center, Hidaka, Japan
  6. 6Ella Lemelbaum Institute for Immuno-Oncology, Sheba Medical Center, Ramat Gan, Israel
  7. 7University of California Irvine, Irvine, USA
  8. 8Oncovida Cancer Center, Providencia, Chile
  9. 9imat Oncomedica S.A., Montería, Colombia
  10. 10Universidad de La Frontera, Temuco, Chile
  11. 11Istanbul Medeniyet University Hospital, Istanbul, Turkey
  12. 12Instituto Nacional de Enfermedades Neoplásicas, Medical Oncology, Lima, Peru
  13. 13Centre Hospitalier de l’Université de Montréal (CHUM), Centre de Recherche de l’Université de Montréal (CRCHUM), Université de Montréal, Montreal, Canada
  14. 14Centre Hospitalier Universitaire de Québec, Université Laval, Québec City, Canada
  15. 15Medical Rehabilitation Center under the Ministry of Health of Russian Federation, Moscow, Russian Federation
  16. 16Merck and Co., Inc., Kenilworth, USA
  17. 17Arizona Oncology (US Oncology Network), University of Arizona College of Medicine, Creighton University School of Medicine, Phoenix, USA


Introduction/Background*Pembrolizumab has efficacy in previously treated, PD-L1-positive advanced cervical cancer. KEYNOTE-826 (NCT03635567) was a phase 3, randomised, double-blind trial of pembrolizumab or placebo added to chemotherapy ± bevacizumab for first-line treatment of recurrent, persistent, or metastatic cervical cancer.

Methodology Eligible adults had persistent, recurrent, or metastatic cervical cancer not previously treated with systemic chemotherapy and not amenable to curative treatment. Patients were randomised 1:1 to pembrolizumab 200 mg or placebo Q3W for ≤35 cycles added to chemotherapy (paclitaxel plus cisplatin or carboplatin) ± bevacizumab and stratified by metastatic status at diagnosis, planned bevacizumab use, and PD-L1 combined positive score (CPS). Dual primary endpoints were PFS (RECIST v1.1, investigator review) and OS tested sequentially in the CPS ≥1, all-comer, and CPS ≥10 populations.

Result(s)*617 patients were randomized: 308 to pembrolizumab plus chemotherapy (63.6% with bevacizumab) and 309 to placebo plus chemotherapy (62.5% with bevacizumab); 548 (88.8%) patients had CPS ≥1, 317 (51.4%) had CPS ≥10. At the protocol-specified first interim analysis, pembrolizumab plus chemotherapy ± bevacizumab significantly improved PFS in the CPS ≥1 (median, 10.4 vs 8.2 months; HR, 0.62 [95% CI, 0.50–0.77]; P<0.001), all-comer (10.4 vs 8.2 months; 0.65 [0.53–0.79]; P<0.001), and CPS ≥10 (10.4 vs 8.1 months; 0.58 [0.44–0.77]; P<0.001) populations. OS was also significantly improved in the CPS ≥1 (median, not reached [NR] vs 16.3 months; HR, 0.64 [95% CI, 0.50–0.81]; P<0.001), all-comer (24.4 vs 16.5 months; 0.67 [0.54–0.84]; P<0.001), and CPS ≥10 (NR vs 16.4 months; 0.61 [0.44–0.84]; P=0.001) populations. Benefits were seen in the with and without bevacizumab subgroups. The incidence of grade ≥3 AEs was 81.8% in the pembrolizumab arm and 75.1% in the placebo arm. Anaemia and neutropenia were the most common grade ≥3 AEs (30.3% vs 26.9% and 12.4% vs 9.7%, respectively).

Conclusion*Pembrolizumab plus chemotherapy ± bevacizumab significantly improves OS and PFS in patients with persistent, recurrent, or metastatic cervical cancer. Along with a manageable safety profile, the clinically meaningful survival benefits suggest pembrolizumab plus chemotherapy ± bevacizumab may be a new standard first-line therapy for this population.

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