Pembrolizumab or Placebo Plus Chemotherapy With or Without Bevacizumab for Persistent, Recurrent, or Metastatic Cervical Cancer
-
Published:2023-12-14
Issue:
Volume:
Page:
-
ISSN:2374-2437
-
Container-title:JAMA Oncology
-
language:en
-
Short-container-title:JAMA Oncol
Author:
Tewari Krishnansu S.1, Colombo Nicoletta2, Monk Bradley J.3, Dubot Coraline4, Cáceres M. Valeria5, Hasegawa Kosei6, Shapira-Frommer Ronnie7, Salman Pamela8, Yañez Eduardo9, Gümüş Mahmut10, Olivera Hurtado de Mendoza Mivael11, Samouëlian Vanessa12, Castonguay Vincent13, Arkhipov Alexander14, Tekin Cumhur15, Li Kan15, Toker Sarper15, Keefe Stephen M.15, Lorusso Domenica16
Affiliation:
1. Obstetrics & Gynecology, University of California, Irvine, Orange 2. Gynecologic Oncology, European Institute of Oncology IRCCS and Università degli Studi di Milano Bicocca, Milan, Italy 3. HonorHealth Research Institute, University of Arizona College of Medicine, Creighton University School of Medicine, Phoenix 4. Oncologie Médicale, Institut Curie Saint Cloud, and GINECO, Paris, France 5. Medical Oncology, Instituto de Oncologia Angel H. Roffo, Buenos Aires, Argentina 6. Gynecologic Oncology, Saitama Medical University International Medical Center, Hidaka, Japan 7. Ella Lemelbaum Institute for Immuno-Oncology, Sheba Medical Center, Ramat Gan, Israel 8. Medical Oncology, Oncovida Cancer Center, Providencia, Santiago, Chile 9. Medical Oncology, Universidad de la Frontera, Temuco, Chile 10. Medical Oncology, Istanbul Medeniyet University Hospital, Istanbul, Turkey 11. Medical Oncology, Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru 12. Gynecologic Oncology, Centre Hospitalier de l’Université de Montréal, Centre de Recherche de l’Université de Montréal, Université de Montréal, Montreal, Quebec, Canada 13. Medical Oncology, Centre Hospitalier Universitaire de Québec, Université Laval, Quebec City, Quebec, Canada 14. Oncology and Chemical Therapy, Medical Rehabilitation Center Under the Ministry of Health of Russian Federation, Moscow, Russian Federation 15. Oncology, Merck & Co, Inc, Rahway, New Jersey 16. Gynaecology Oncology Unit, Fondazione Policlinico Universitario A Gemelli IRCCS and Catholic University of Sacred Heart, Rome, Italy
Abstract
ImportanceThe KEYNOTE-826 randomized clinical trial showed statistically significant and clinically meaningful survival benefits with the addition of pembrolizumab to chemotherapy with or without bevacizumab in patients with persistent, recurrent, or metastatic cervical cancer. Treatment effects in patient subgroups of the study population are unknown.ObjectiveTo assess efficacy outcomes in patient subgroups of KEYNOTE-826.Design, Setting, and ParticipantsExploratory subgroup analyses were conducted in a global, phase 3, randomized, double-blind, placebo-controlled clinical trial. Participants included women with persistent, recurrent, or metastatic adenocarcinoma, adenosquamous carcinoma, or squamous cell carcinoma of the cervix that had not been treated with systemic chemotherapy and was not amenable to curative treatment. This subanalysis was conducted from November 20, 2018, to May 3, 2021.InterventionsPembrolizumab, 200 mg, every 3 weeks or placebo for up to 35 cycles plus chemotherapy (paclitaxel, 175 mg/m2, plus cisplatin, 50 mg/m2, or carboplatin AUC 5 [area under the free carboplatin plasma concentration vs time curve]) with or without bevacizumab, 15 mg/kg.Main Outcomes and MeasuresOverall survival (OS) and progression-free survival (PFS) by investigator assessment per Response Evaluation Criteria in Solid Tumors version 1.1 in subgroups defined by use of bevacizumab (yes or no), choice of platinum (carboplatin or cisplatin), prior chemoradiotherapy (CRT) exposure only (yes or no), and histologic type (squamous or nonsquamous) in patients with programmed cell death ligand 1–positive tumors (defined as a combined positive score [CPS] ≥1) and in the intention-to-treat population.ResultsA total of 617 patients (median age, 51 years; range, 22-82 years) were enrolled in the trial. In the CPS greater than or equal to 1 population, hazard ratios (HRs) for OS favored the pembrolizumab group in all subgroups: with bevacizumab (HR, 0.62; 95% CI, 0.45-0.87) and without bevacizumab (HR, 0.67; 95% CI, 0.47-0.96), use of carboplatin (HR, 0.65; 95% CI, 0.50-0.85) and cisplatin (HR, 0.53; 95% CI, 0.27-1.04), with prior CRT only (HR, 0.56; 95% CI, 0.39-0.81) and without prior CRT only (HR, 0.72; 95% CI, 0.52-1.00), and squamous (HR, 0.60; 95% CI, 0.46-0.79) and nonsquamous (HR, 0.70; 95% CI, 0.41-1.20) histologic type. In the intention-to-treat population, HRs for OS also favored the pembrolizumab group in all subgroups: with bevacizumab (HR, 0.63; 95% CI, 0.47-0.87) and without bevacizumab (HR, 0.74; 95% CI, 0.53-1.04), use of carboplatin (HR, 0.69; 95% CI, 0.54-0.89) or cisplatin (HR, 0.59; 95% CI, 0.32-1.09), with prior CRT only (HR, 0.64; 95% CI, 0.45-0.91) and without prior CRT only (HR, 0.71; 95% CI, 0.53-0.97), and squamous (HR, 0.61; 95% CI, 0.47-0.80) and nonsquamous (HR, 0.76; 95% CI, 0.47-1.23) histologic type. Similar to OS, the addition of pembrolizumab prolonged PFS across all subgroups in the CPS greater than or equal to 1 and intention-to-treat populations.Conclusions and RelevanceThe findings of this trial suggest that adding pembrolizumab to chemotherapy with or without bevacizumab improved OS across subgroups of patients with persistent, recurrent, or metastatic cervical cancer.Trial RegistrationClinicalTrials.gov Identifier: NCT03635567
Publisher
American Medical Association (AMA)
Subject
Oncology,Cancer Research
Reference22 articles.
1. Cancer statistics, 2023.;Siegel;CA Cancer J Clin,2023 2. Improved survival with bevacizumab in advanced cervical cancer.;Tewari;N Engl J Med,2014 3. Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240).;Tewari;Lancet,2017 4. Pembrolizumab for persistent, recurrent, or metastatic cervical cancer.;Colombo;N Engl J Med,2021 5. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects.;World Medical Association;JAMA,2013
|
|