TY - JOUR
T1 - Pembrolizumab plus olaparib in patients with metastatic castration-resistant prostate cancer
T2 - long-term results from the phase 1b/2 KEYNOTE-365 Cohort A study
AU - Yu, Evan Y.
AU - Piulats, Josep M.
AU - Gravis, Gwenaelle
AU - Fong, Peter C. C.
AU - Todenhöfer, Tilman
AU - Laguerre, Brigitte
AU - Arranz, Jose A.
AU - Oudard, Stephane
AU - Massard, Christophe
AU - Heinzelbecker, Julia
AU - Nordquist, Luke T.
AU - Carles, Joan
AU - Kolinsky, Michael P.
AU - Augustin, Marinela
AU - Gurney, Howard
AU - Tafreshi, Ali
AU - Li, Xin Tong
AU - Qiu, Ping
AU - Poehlein, Christian H.
AU - Schloss, Charles
AU - de Bono, Johann S.
N1 - Copyright Merck Sharp & Dohme LLC., a subsidiary Merck & Co., Inc., Rahway, NJ, USA and the Author(s) 2022. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.
A corrigendum exists for the supplementary files of this article, and the online version has been updated. The corrigendum can be found at DOI: 10.1016/j.eururo.2022.11.025
PY - 2023/1
Y1 - 2023/1
N2 - Background: Pembrolizumab and olaparib have shown single-agent activity in patients with previously treated metastatic castration-resistant prostate cancer (mCRPC). Objective: To evaluate the efficacy and safety of pembrolizumab plus olaparib in mCRPC. Design, setting, and participants: 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. Intervention: Pembrolizumab 200 mg intravenously every 3 wk plus olaparib 400-mg capsule or 300-mg tablet orally twice daily. Outcome measurements and statistical analysis: 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). Results and limitations: 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. Conclusions: 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. Patient summary: Pembrolizumab plus olaparib showed antitumor activity and expected safety in patients with metastatic castration-resistant prostate cancer.
AB - Background: Pembrolizumab and olaparib have shown single-agent activity in patients with previously treated metastatic castration-resistant prostate cancer (mCRPC). Objective: To evaluate the efficacy and safety of pembrolizumab plus olaparib in mCRPC. Design, setting, and participants: 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. Intervention: Pembrolizumab 200 mg intravenously every 3 wk plus olaparib 400-mg capsule or 300-mg tablet orally twice daily. Outcome measurements and statistical analysis: 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). Results and limitations: 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. Conclusions: 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. Patient summary: Pembrolizumab plus olaparib showed antitumor activity and expected safety in patients with metastatic castration-resistant prostate cancer.
KW - Metastatic castration-resistant prostate cancer
KW - Olaparib
KW - Pembrolizumab
UR - http://www.scopus.com/inward/record.url?scp=85137032851&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/record.url?scp=85144754327&partnerID=8YFLogxK
UR - https://doi.org/10.1016/j.eururo.2022.11.025
U2 - 10.1016/j.eururo.2022.08.005
DO - 10.1016/j.eururo.2022.08.005
M3 - Article
C2 - 36055895
AN - SCOPUS:85137032851
SN - 0302-2838
VL - 83
SP - 15
EP - 26
JO - European Urology
JF - European Urology
IS - 1
ER -