TY - JOUR
T1 - Pembrolizumab Plus Olaparib for Patients With Previously Treated and Biomarker-Unselected Metastatic Castration-Resistant Prostate Cancer
T2 - The Randomized, Open-Label, Phase III KEYLYNK-010 Trial
AU - Antonarakis, Emmanuel S.
AU - Park, Se Hoon
AU - Goh, Jeffrey C.
AU - Shin, Sang Joon
AU - Lee, Jae Lyun
AU - Mehra, Niven
AU - Mcdermott, Ray
AU - Sala-Gonzalez, Núria
AU - Fong, Peter C.
AU - Greil, Richard
AU - Retz, Margitta
AU - Sade, Juan Pablo
AU - Yanez, Patricio
AU - Huang, Yi Hsiu
AU - Begbie, Stephen D.
AU - Gafanov, Rustem Airatovich
AU - De Santis, Maria
AU - Rosenbaum, Eli
AU - Kolinsky, Michael P.
AU - Rey, Felipe
AU - Chiu, Kun Yuan
AU - Roubaud, Guilhem
AU - Kramer, Gero
AU - Sumitomo, Makoto
AU - Massari, Francesco
AU - Suzuki, Hiroyoshi
AU - Qiu, Ping
AU - Zhang, Jinchun
AU - Kim, Jeri
AU - Poehlein, Christian H.
AU - Yu, Evan Y.
N1 - Publisher Copyright:
© American Society of Clinical Oncology.
PY - 2023/8/1
Y1 - 2023/8/1
N2 - PURPOSEThere is an unmet need for therapeutic options that prolong survival for patients with heavily pretreated, metastatic castration-resistant prostate cancer (mCRPC). The phase III, open-label KEYLYNK-010 study evaluated pembrolizumab plus olaparib versus a next-generation hormonal agent (NHA) for biomarker-unselected, previously treated mCRPC.METHODSEligible participants had mCRPC that progressed on or after abiraterone or enzalutamide (but not both) and docetaxel. Participants were randomly assigned (2:1) to pembrolizumab plus olaparib or NHA (abiraterone or enzalutamide). The dual primary end points were radiographic progression-free survival (rPFS) by blinded independent central review per Prostate Cancer Working Group-modified RECIST 1.1 and overall survival (OS). Time to first subsequent therapy (TFST) was a key secondary end point. Safety and objective response rate (ORR) were secondary end points.RESULTSBetween May 30, 2019, and July 16, 2021, 529 participants were randomly assigned to pembrolizumab plus olaparib and 264 to NHA. At final rPFS analysis, median rPFS was 4.4 months (95% CI, 4.2 to 6.0) with pembrolizumab plus olaparib and 4.2 months (95% CI, 4.0 to 6.1) with NHA (hazard ratio [HR], 1.02 [95% CI, 0.82 to 1.25]; P =.55). At final OS analysis, median OS was 15.8 months (95% CI, 14.6 to 17.0) and 14.6 months (95% CI, 12.6 to 17.3), respectively (HR, 0.94 [95% CI, 0.77 to 1.14]; P =.26). At final TFST analysis, median TFST was 7.2 months (95% CI, 6.7 to 8.1) versus 5.7 months (95% CI, 5.0 to 7.1), respectively (HR, 0.86 [95% CI, 0.71 to 1.03]). ORR was higher with pembrolizumab plus olaparib versus NHA (16.8% v 5.9%). Grade ≥3 treatment-related adverse events occurred in 34.6% and 9.0% of participants, respectively.CONCLUSIONPembrolizumab plus olaparib did not significantly improve rPFS or OS versus NHA in participants with biomarker-unselected, heavily pretreated mCRPC. The study was stopped for futility. No new safety signals occurred.
AB - PURPOSEThere is an unmet need for therapeutic options that prolong survival for patients with heavily pretreated, metastatic castration-resistant prostate cancer (mCRPC). The phase III, open-label KEYLYNK-010 study evaluated pembrolizumab plus olaparib versus a next-generation hormonal agent (NHA) for biomarker-unselected, previously treated mCRPC.METHODSEligible participants had mCRPC that progressed on or after abiraterone or enzalutamide (but not both) and docetaxel. Participants were randomly assigned (2:1) to pembrolizumab plus olaparib or NHA (abiraterone or enzalutamide). The dual primary end points were radiographic progression-free survival (rPFS) by blinded independent central review per Prostate Cancer Working Group-modified RECIST 1.1 and overall survival (OS). Time to first subsequent therapy (TFST) was a key secondary end point. Safety and objective response rate (ORR) were secondary end points.RESULTSBetween May 30, 2019, and July 16, 2021, 529 participants were randomly assigned to pembrolizumab plus olaparib and 264 to NHA. At final rPFS analysis, median rPFS was 4.4 months (95% CI, 4.2 to 6.0) with pembrolizumab plus olaparib and 4.2 months (95% CI, 4.0 to 6.1) with NHA (hazard ratio [HR], 1.02 [95% CI, 0.82 to 1.25]; P =.55). At final OS analysis, median OS was 15.8 months (95% CI, 14.6 to 17.0) and 14.6 months (95% CI, 12.6 to 17.3), respectively (HR, 0.94 [95% CI, 0.77 to 1.14]; P =.26). At final TFST analysis, median TFST was 7.2 months (95% CI, 6.7 to 8.1) versus 5.7 months (95% CI, 5.0 to 7.1), respectively (HR, 0.86 [95% CI, 0.71 to 1.03]). ORR was higher with pembrolizumab plus olaparib versus NHA (16.8% v 5.9%). Grade ≥3 treatment-related adverse events occurred in 34.6% and 9.0% of participants, respectively.CONCLUSIONPembrolizumab plus olaparib did not significantly improve rPFS or OS versus NHA in participants with biomarker-unselected, heavily pretreated mCRPC. The study was stopped for futility. No new safety signals occurred.
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U2 - 10.1200/JCO.23.00233
DO - 10.1200/JCO.23.00233
M3 - Article
C2 - 37290035
AN - SCOPUS:85166364089
SN - 0732-183X
VL - 41
SP - 3839
EP - 3850
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 22
ER -