Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2022

Pembrolizumab plus chemotherapy in persistent, recurrent, or metastatic cervical cancer: a KEYNOTE-826 subgroup analysis (#188)

Sally Baron-Hay 1 , Krishnansu S. Tewari 2 , Nicoletta Colombo 3 , Bradley J. Monk 4 , Coraline Dubot 5 , M. Valeria Cáceres 6 , Kosei Hasegawa 7 , Ronnie Shapira-Frommer 8 , Pamela Salman 9 , Eduardo Yañez 10 , Mahmut Gümüş 11 , Mivael Olivera Hurtado de Mendoza 12 , Vanessa Samouëlian 13 , Vincent Castonguay 14 , Alexander Arkhipov 15 , Sophia Frentzas 16 , Cumhur Tekin 17 , Kan Li 17 , Sarper Toker 17 , Stephen M. Keefe 17 , Domenica Lorusso 18
  1. Northern Sydney Cancer Center, Royal North Shore Hospital, St Leonards, NSW, Australia
  2. Obstetrics & Gynecology, University of California, Irvine, Orange, CA, USA
  3. Gynecologic Oncology, European Institute of Oncology IRCCS and Università degli Studi di Milano Bicocca, Milan, Italy
  4. Gynecologic Oncology, University of Arizona College of Medicine, Creighton University School of Medicine, Phoenix, AZ, USA
  5. Oncologie Médicale, Institut Curie Saint Cloud, and GINECO, Paris, France
  6. Medical Oncology, Instituto de Oncologia Angel H. Roffo, Buenos Aires, Argentina
  7. Gynecologic Oncology, Saitama Medical University International Medical Center, Hidaka, Japan
  8. Ella Lemelbaum Institute for Immuno-Oncology, Sheba Medical Center, Ramat Gan, Israel
  9. Medical Oncology, Oncovida Cancer Center, Providencia, Santiago, Chile
  10. Medical Oncology, Universidad de la Frontera, Temuco, Chile
  11. Istanbul Medeniyet University, Prof. Dr. Suleyman Yalcin City Hospital, Istanbul, Turkey
  12. Medical Oncology, Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru
  13. Gynecologic Oncology, Centre Hospitalier de l’Université de Montréal (CHUM), Centre de Recherche de l’Université de Montréal (CRCHUM), Université de Montréal, Montreal, QC, Canada
  14. Medical Oncology, Centre Hospitalier Universitaire de Québec, Université Laval, Quebec City, QC, Canada
  15. Oncology and Chemical Therapy, Medical Rehabilitation Center under the Ministry of Health of Russian Federation, Moscow, Russian Federation
  16. Monash Health, Monash Medical Centre, Clayton, VIC, Australia
  17. Oncology, Merck & Co., Inc., Kenilworth, NJ, USA
  18. Gynaecology Oncology Unit, Fondazione Policlinico Universitario A Gemelli IRCCS and Catholic University of Sacred Heart, Rome, Italy

Aims: In KEYNOTE-826 (NCT03635567), pembrolizumab+chemotherapy±bevacizumab provided statistically significant, clinically meaningful PFS and OS improvements in persistent, recurrent, or metastatic cervical cancer. We present outcomes in key subgroups.

Methods: Eligible adults had persistent, recurrent, or metastatic cervical cancer not previously treated with chemotherapy nor amenable to curative treatment; measurable disease (RECIST v1.1); ECOG PS 0–1; and a tumor sample for PD-L1 assessment. Patients were randomized 1:1 to pembrolizumab 200 mg Q3W or placebo (up to 35 cycles)+chemotherapy (paclitaxel 175 mg/m2+cisplatin 50 mg/m2 or carboplatin AUC 5)±bevacizumab 15 mg/kg. Dual primary endpoints were PFS by investigator (RECIST v1.1) and OS in patients with PD-L1 CPS ≥1, all comers, and CPS ≥10. Results were examined in subgroups defined by bevacizumab use, histology, platinum use, and prior chemoradiation therapy (CRT).

Results: 617 patients were randomized (pembrolizumab+chemotherapy±bevacizumab, n=308; placebo+chemotherapy±bevacizumab, n=309). At data cutoff (May 3, 2021), median follow-up was 22 months. In all comers, pembrolizumab+chemotherapy±bevacizumab prolonged PFS and OS vs placebo+chemotherapy±bevacizumab in all subgroups. In bevacizumab-treated patients, PFS HR (95% CI) was 0.61 (0.47–0.79) and OS HR was 0.63 (0.47–0.87); without bevacizumab, 0.74 (0.54–1.01) and 0.74 (0.53–1.04). For squamous histology, PFS HR was 0.63 (0.50–0.80) and OS HR was 0.61 (0.47–0.80); for nonsquamous, 0.66 (0.43–1.00) and 0.76 (0.47–1.23). For carboplatin-treated patients, PFS HR was 0.69 (0.55–0.86) and OS HR was 0.69 (0.54–0.89); with cisplatin, 0.47 (0.28–0.77) and 0.59 (0.32–1.09). For patients with prior CRT, PFS HR was 0.62 (0.45–0.86) and OS HR was 0.64 (0.45–0.91). Similar benefits of pembrolizumab+chemotherapy±bevacizumab were seen in the CPS ≥1 and CPS ≥10 populations.

Conclusions: Pembrolizumab+chemotherapy±bevacizumab prolonged PFS and OS vs placebo+chemotherapy±bevacizumab in key subgroups and provided clinically meaningful benefits similar to the broader population with persistent, recurrent, or metastatic cervical cancer.