Limited responses have been observed in patients treated with enzalutamide after disease progression on abiraterone for metastatic castration-resistant prostate cancer (mCRPC), but androgen receptor signaling impacts T-cell function.
To evaluate the efficacy and safety of pembrolizumab plus enzalutamide in mCRPC.
Patients in cohort C of the phase 1b/2 KEYNOTE-365 study, who received ≥4 wk of treatment with abiraterone acetate in the prechemotherapy mCRPC state and experienced treatment failure or became drug-intolerant, were included.
Pembrolizumab 200 mg intravenously every 3 wk plus enzalutamide 160 mg orally once daily.
The primary endpoints were safety, the confirmed prostate-specific antigen (PSA) response rate, and the objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors version 1.1 on blinded independent central review (BICR). Secondary endpoints included radiographic progression-free survival (rPFS) on BICR and overall survival (OS).
A total of 102 patients received pembrolizumab plus enzalutamide. Median follow-up was 51 mo (interquartile range 37-56). The confirmed PSA response rate was 24% (95% confidence interval [CI] 16-33%). The confirmed ORR was 11% (95% CI 2.9-25%; 4/38 patients; two complete responses). Median rPFS was 6.0 mo (95% CI 4.1-6.3). Median OS was 20 mo (95% CI 17-24). Treatment-related adverse events (TRAEs) occurred in 94 patients (92%); grade 3-5 TRAEs occurred in 44 patients (43%). The incidence of treatment-related rash was higher with combination therapy than expected from the safety profile of each drug. One patient (1.0%) died of a TRAE (cause unknown). Study limitations include the single-arm design.
Pembrolizumab plus enzalutamide had limited antitumor activity in patients who received prior abiraterone treatment without previous chemotherapy for mCRPC, with a safety profile consistent with the individual profiles of each agent.
Pembrolizumab plus enzalutamide showed limited antitumor activity and manageable safety in patients with metastatic castration-resistant prostate cancer. The KEYNOTE-365 trial is registered on ClinicalTrials.gov as NCT02861573.
European urology oncology. 2023 Nov 06 [Epub ahead of print]
Evan Y Yu, William R Berry, Howard Gurney, Margitta Retz, Henry J Conter, Brigitte Laguerre, Peter C C Fong, Cristiano Ferrario, Tilman Todenhöfer, Gwenaelle Gravis, Josep M Piulats, Urban Emmenegger, Neal D Shore, Emanuela Romano, Loic Mourey, Xin Tong Li, Christian H Poehlein, Charles Schloss, Leonard J Appleman, Johann S de Bono
Division of Hematology and Oncology, Fred Hutchinson Cancer Center and University of Washington, Seattle, WA, USA. Electronic address: ., Duke Cancer Center Cary, Cary, NC, USA., Department of Clinical Medicine, Macquarie University, Sydney, Australia., University Hospital Rechts der Isar, Technical University of Munich, Munich, Germany., University of Western Ontario, Brampton, Canada., Center Eugène Marquis, Rennes, France., Aukland City Hospital and the University of Aukland., Jewish General Hospital, Montreal, Canada., Studienpraxis Urologie, Nürtingen, Germany., Institut Paoli-Calmettes, Marseille, France., Catalan Institute of Oncology, Barcelona, Spain., Division of Medical Oncology, Odette Cancer Centre, Toronto, Canada., Carolina Urologic Research Center, Myrtle Beach, SC, USA., Department of Oncology, Center for Cancer Immunotherapy, Institut Curie, Paris, France., Department of Medical Oncology, Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France., MSD China, Beijing, China., Merck & Co., Inc., Rahway, NJ, USA., UPMC Hillman Cancer Center, Pittsburgh, PA, USA., The Institute of Cancer Research, The Royal Marsden Hospital, London, UK.