Pembrolizumab and olaparib have shown single-agent activity in patients with previously treated metastatic castration-resistant prostate cancer (mCRPC).
To evaluate the efficacy and safety of pembrolizumab plus olaparib in mCRPC.
Cohort A of the phase 1b/2 KEYNOTE-365 study enrolled patients with molecularly unselected, docetaxel-pretreated mCRPC whose disease progressed within 6 mo of screening.
Pembrolizumab 200 mg intravenously every 3 wk plus olaparib 400-mg capsule or 300-mg tablet orally twice daily.
The primary endpoints were safety, confirmed prostate-specific antigen (PSA) response rate, and objective response rate (ORR) as per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, by blinded independent central review. The secondary endpoints included radiographic progression-free survival (rPFS) and overall survival (OS).
Of 104 enrolled patients, 102 were treated. The median age was 70 yr (interquartile range [IQR], 65-76), and 59 patients (58%) had measurable disease as per RECIST v1.1. The median time from the first dose to database cutoff was 24 mo (IQR, 22-47). The confirmed PSA response rate was 15%. The confirmed ORR was 8.5% (five partial responses) for patients with measurable disease. The median rPFS was 4.5 mo (95% confidence interval [CI], 4.0-6.5) and median OS was 14 mo (95% CI, 10.4-18.2). Clinical activity was consistent across the programmed death ligand 1 (PD-L1)-positive and homologous recombination repair mutation subgroups. Treatment-related adverse events (TRAEs) occurred in 93 patients (91%). Grade 3-5 TRAEs occurred in 49 patients (48%). Six deaths (5.9%) were due to adverse events; two (myocardial infarction and unknown cause) were attributed to treatment. Limitations of the study include the single-arm design.
Pembrolizumab plus olaparib had a safety profile consistent with the profiles of the individual agents and demonstrated antitumor activity in previously treated patients with molecularly unselected, docetaxel-pretreated mCRPC.
Pembrolizumab plus olaparib showed antitumor activity and expected safety in patients with metastatic castration-resistant prostate cancer.
European urology. 2022 Aug 30 [Epub ahead of print]
Evan Y Yu, Josep M Piulats, Gwenaelle Gravis, Peter C C Fong, Tilman Todenhöfer, Brigitte Laguerre, Jose A Arranz, Stephane Oudard, Christophe Massard, Julia Heinzelbecker, Luke T Nordquist, Joan Carles, Michael P Kolinsky, Marinela Augustin, Howard Gurney, Ali Tafreshi, Xin Tong Li, Ping Qiu, Christian H Poehlein, Charles Schloss, Johann S de Bono
University of Washington and Fred Hutchinson Cancer Center, Seattle, WA, USA. Electronic address: ., Catalan Institute of Oncology, Barcelona, Spain., Institut Paoli Calmettes, Marseille, France., Auckland City Hospital, Auckland, New Zealand; University of Auckland, Auckland, New Zealand., Studienpraxis Urologie, Nürtingen, Germany., Centre Eugène Marquis, Rennes, France., General University Hospital Gregorio Marañón, Madrid, Spain., Hôpital Européen Georges Pompidou, University of Paris, Paris, France., Gustave Roussy, Cancer Campus, Villejuif, France; Paris-Saclay University, Villejuif, France., Saarland University Medical Center, Homburg, Germany; Faculty of Medicine, Saarland University, Homburg, Germany., GU Research Network-Urology Cancer Center, Omaha, NE, USA., Vall d'Hebron Institute of Oncology, Vall d'Hebron, Barcelona, Spain., Cross Cancer Institute and University of Alberta, Edmonton, AB, Canada., Paracelsus Medical University, Nuremberg, Germany., Macquarie University, Sydney, Australia., University of Wollongong, Wollongong, NSW, Australia., Merck & Co., Inc., Rahway, NJ, USA., The Institute of Cancer Research and the Royal Marsden, London, UK.