Abiraterone acetate (abiraterone) plus prednisone is approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Our aim was to evaluate the efficacy and safety of pembrolizumab plus abiraterone in mCRPC.
In cohort D of the phase 1b/2 KEYNOTE-365 study (NCT02861573), patients were chemotherapy-naïve, had disease progression ≤6 mo before screening, and had either not received prior next-generation hormonal agents for mCRPC or had received prior enzalutamide for mCRPC and had disease progression or became intolerant to enzalutamide. Patients received pembrolizumab 200 mg intravenously every 3 wk plus abiraterone 1000 mg orally once daily and prednisone 5 mg orally twice daily. The primary endpoints were safety, prostate-specific antigen (PSA) response rate, and objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by blinded independent central review (BICR). Secondary endpoints included radiographic progression-free survival (rPFS) according to Prostate Cancer Clinical Trials Working Group 3-modified RECIST v1.1 by BICR and overall survival (OS).
For the 103 patients who were treated, median follow-up was 28 mo (interquartile range 26-31). The confirmed PSA response rate was 56% (58/103 patients). The ORR for patients with RECIST v1.1-measurable disease was 16% (6/37 patients). Median rPFS was 15 mo (95% confidence interval 9.2-22) and median OS was 30 mo (95% confidence interval 23-not reached); the estimated 24-mo OS rate was 58%. In total, 91% of patients experienced treatment-related adverse events, and 39% experienced grade 3-5 events. Grade 3/4 elevation of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) was observed in 12% and 6.8% of patients, respectively. One patient died due to treatment-related myasthenic syndrome. Study limitations include the single-arm design.
Pembrolizumab plus abiraterone and prednisone demonstrated antitumor activity and acceptable safety in patients with chemotherapy-naïve mCRPC. Higher incidence of grade 3/4 elevated ALT/AST occurred than was reported for the individual agents.
For patients with metastatic castratation-resistant prostate cancer, the drug combination of pembrolizumab plus abiraterone and prednisone showed antitumor activity and acceptable safety.
European urology oncology. 2024 Jun 25 [Epub ahead of print]
Evan Y Yu, Cristiano Ferrario, Mark D Linch, Michael Stoeckle, Brigitte Laguerre, Jose A Arranz, Tilman Todenhöfer, Peter C Fong, Josep M Piulats, William Berry, Urban Emmenegger, Loic Mourey, Anthony M Joshua, Nataliya Mar, Leonard J Appleman, Henry J Conter, Gwenaelle Gravis, Xin Tong Li, Charles Schloss, Christian Poehlein, Johann S de Bono
Fred Hutchinson Cancer Center and University of Washington, Seattle, WA, USA. Electronic address: ., Jewish General Hospital, Montreal, Canada., University College London Hospital, London, UK., Saarland University, Homburg, Germany., Eugene Marquis Center, Rennes, France., Gregorio Marañón University Hospital, Madrid, Spain., Studienpraxis Urologie, Nürtingen, Germany., Auckland City Hospital and University of Auckland, Auckland, New Zealand., Catalan Institute of Oncology, Barcelona, Spain., Duke Cancer Center Cary, Cary, NC, USA., Sunnybrook Research Institute, Toronto, Canada., IUCT-Oncopole Claudius Regaud, Toulouse, France., St Vincent's Hospital Sydney, Sydney, Australia., UCI Health, Orange, CA, USA., University of Pittsburgh Medical Center, Pittsburgh, PA, USA., William Osler Health System, Brampton, Canada., Institut Paoli-Calmettes, Marseille, France., Merck & Co. Inc, Rahway, NJ, USA., Royal Marsden NHS Foundation Trust, London, UK.