Review Article

BRCA Mutations in Prostate Cancer: Prognostic and Predictive Implications

Table 1

Ongoing clinical trials assessing the role of PARPi in mCRPC.

Clinical trialPhaseStudy drugStrategyPrimary endpoint

NCT02861573IOlaparibPembrolizumab + olaparib in postdocetaxel settingRR (PSA50)
NCT03874884IOlaparibOlaparib + 177Lu-PSMA in mCRPCDLTs, MTD, RP2D
NCT03205176IOlaparibOlaparib ± AZD5153 (BRD4/BET bromodomain inhibitor) in mCRPCDLT
NCT02484404I/IIOlaparibOlaparib ± ceridanib ± MEDI4736 (anti-PD-1) in mCRPCRP2D, AE
NCT03317392I/IIOlaparibRa223 ± olaparib in mCRPC patients with bone metastasesMTD, rPFS
NCT03787680IIOlaparibOlaparib + ATR inhibitor (AZD6738) in second-line settingRR
NCT03012321IIOlaparibOlaparib ± abiraterone/prednisone in first-line settingPFS
NCT03434158IIOlaparibOlaparib for patients who are responding after docetaxel chemotherapyrPFS
NCT03263650IIOlaparibOlaparib for patients who are responding after cabazitaxel plus carboplatinPFS
NCT03516812IIOlaparibOlaparib + testosterone enanthate in postabiraterone/enzalutamide settingRR (PSA50)
NCT02893917IIOlaparibOlaparib ± cediranib in second-line settingrPFS
NCT03732820IIIOlaparibAbiraterone/prednisone ± olaparib in first-line settingrPFS
NCT03834519IIIOlaparibOlaparib plus pembrolizumab versus abiraterone acetate or enzalutamide after chemotherapy and ARSiOS and PFS
NCT03076203INiraparibNiraparib + radium-223MTD
NCT03431350I/IINiraparibNiraparib + abiraterone/prednisone or JNJ-63723283 in post-ARSi settingAE, ORR
NCT02854436IINiraparibNiraparib in postdocetaxel and post-ARSi settingsORR
NCT03748641IIINiraparibAbiraterone/prednisone ± niraparib in first-line settingrPFS
NCT04179396IRucaparibRucaparib + abiraterone or enzalutamide in mCRPCPK, AE
NCT03840200IRucaparibRucaparib + ipatasertib in mCRPC after ARSiAE, DLTs, PSA response
NCT04253262I/IIRucaparibRucaparib + copanlisib (PI3K inhibitor) in mCRPC progressing after ARSiMTD, ORR
NCT03840200I/IIRucaparibRucaparib + ipatasertib after ARSiAE, DLT, RR (PSA)
NCT03572478I/IIRucaparibRucaparib vs. rucaparib + nivolumab vs. nivolumabDLT
NCT02952534IIRucaparibRucaparib in postdocetaxel and post-ARSi settingsORR
NCT03338790IIRucaparibNivolumab + rucaparib or docetaxel or enzalutamideORR
NCT03442556IIRucaparibRucaparib for patients who are responding after docetaxel plus carboplatinrPFS
NCT02975934IIIRucaparibRucaparib vs. abiraterone/enzalutamide/docetaxel in second-line settingrPFS
NCT04019327I/IITalazoparibTalazoparib + temozolomide in mCRPC without DNA damage repair mutation after at least one ARSiAE, ORR
NCT04052204I/IITalazoparibTalazoparib + avelumab + bempegaldesleukin in mCRPCDLT, ORR
NCT03330405IITalazoparibAvelumab plus talazoparib in advanced solid tumorsDLT, ORR
NCT03148795IITalazoparibTalazoparib in postdocetaxel and postabiraterone/enzalutamide settingsORR
NCT03395197IIITalazoparibEnzalutamide ± talazaparib in first-line settingrPFS
NCT04182516INMS-03305293NMS-03305293 (PARP inhibitor) in mCRPCFirst cycle DLTs

RR: response rate; PSA50: decline in PSA level ≥50% than baseline; MTD: maximum tolerated dose; rPFS: radiological progression-free survival; PFS: progression-free survival; OS: overall survival; AE: adverse events; ORR: objective response rate; DLT: dose-limiting toxicities; MTD: maximum tolerated dose; RP2D: recommended phase II dose; and PK: pharmacokinetic.