Table 1.
Phase II or III trials using PARP inhibitors alone to treat prostate cancers
| CTID | Treatment | Phase | No. patients or estimated enrollment | Disease status | Mandatory HRR status for inclusion | Determination method for HRD | Primary endpoints | Results |
|---|---|---|---|---|---|---|---|---|
| NCT01682772/TOPARP-A | Olaparib | 2 | 50 | mCRPC after at least docetaxel | No | Tumor | Composite response rateb |
All comers: 33% HRD: 88% |
| NCT01682772/TOPARP-B | Olaparib | 2 | 98 | mCRPC after at least docetaxel | Bi-allelic deleterious HRD | Tumor |
Composite response rateb Preplanned secondary endpoint: ORR |
BRCA1/2: 83%, ORR: 52.4% PALB2: 57%, ORR: 33.3% ATM: 37%, ORR: 8.3% CDK12: 25%, ORR: 0% |
| NCT02987543/PROfound | Olaparib versus NHT | 3 | 778 | mCRPC after at least 1 NHT | Bi- or mono-allelic somatic or germline deleterious HRD | Tumor |
Radiographic PFS Preplanned secondary endpoint: OS |
rPFS: BRCA/ATM: 7.4 months versus 3.6mo, HR = 0.34 (95% CI 0.25–0.47) General HRD: 5.8 months versus 3.5 months, HR = 0.49 (95% CI 0.38–0.63) OS: BRCA/ATM: 19.1 months versus 14.7 months HR = 0.69 (CI 95% 0.5–0.97) No-BRCA/ATM: 14.1 months versus 11.5 months HR = 0.96 (CI 95% 0.63–1.49) |
| NCT03432897/BrUOG-337 | Olaparib | 2 | 13 | High-risk localized PC | Deleterious HRDa | Tumor or plasma | PSA response rate prior prostatectomy | Recruiting |
| NCT03047135 | Olaparib | 2 | 50 | Castration Sensitive Biochemically Recurrent nmPC | No | Undescribed method | PSA response rate | Recruiting |
| NCT03434158 /IMANOL | Olaparib as maintenance therapy after docetaxel | 2 | 27 | mCRPC after at least docetaxel | Deleterious HRDa | Undescribed method | Radiographic PFS | Recruiting |
| NCT03012321/BRCAAway | Olaparib versus abiraterone versus abiraterone + olaparib | 2 | 70 | mCRPC, 1st line | No | Tumor | PFS | Recruiting |
| NCT03263650 | Olaparib maintenance after cabazitaxel–carboplatin combination | 2 | 123 | Aggressive variant PC | No | Not performed | PFS | Ongoing, not recruiting |
| NCT02854436/GALAHAD | Niraparib | 2 | 291 | mCRPC after at least 1 chemotherapy and 1 NHT | Bi-allelic HRD or germline pathogenic BRCA1/2 alterationb | Tumor or plasma | ORR |
BRCA: 41% Non-BRCA: 9% |
| NCT04288687 | Niraparib | 2 | 18 | mCRPC, platine sensitivity | Deleterious HRDa | Undescribed method | Radiographic PFS | Not yet recruiting |
| NCT04037254 | ADT (24 months) + RT + niraparib (12 months) | 2 | 180 | High-risk localized PC | No | Not performed | Disease-free survival | Ongoing, not recruiting |
| NCT04030559 | Niraparib for 3 months | 2 | 30 | High-risk localized PC, prior prostatectomy | Bi- or mono-allelic deleterious HRD | Undescribed method | Pathologic response rate | Recruiting |
| NCT02952534/TRITON-2 | Rucaparib | 2 | 193 | mCRPC after at least 1 chemotherapy and 1 NHT | Bi- or mono-allelic somatic or germline deleterious HRD | Tumor or plasma | ORR and PSA response rate (PRR) |
sBRCA1/2: 43.9%, PRR: 50.7% gBRCA1/2: 42.9%, PRR: 61.4% ATM: 10.5%, PRR: 4.1% CDK12: 0%, PRR: 6.7% CHEK12: 11.1%, PRR: 16.7% |
| NCT02975934/TRITON-3 | Rucaparib versus NHT or docetaxel | 3 | 400 | mCRPC, after 1 NHT, 0 chemotherapy | Deleterious BRCA1/2 or ATM alterationa | Undescribed method | Radiographic PFS | Recruiting |
| NCT03413995/TRIUMPH | Rucaparib | 2 | 30 | mCSPC unfit/unwilling ADT | Germline HRD alterationb | Undescribed method | PSA response rate | Recruiting |
| NCT03442556/PLATI-PARP | Rucaparib maintenance after docetaxel–carboplatin combination | 2 | 20 | mCRPC | Bi- or mono-allelic deleterious HRD | Tumor or plasma | Radiographic PFS | Recruiting |
| NCT03533946/ROAR | Rucaparib | 2 | 32 | nmCSPC | Deleterious HRDa | Tumor or plasma | PSA response rate | Recruiting |
| NCT03148795/TALAPRO-1 | Talazoparib | 2 | 100 | mCRPC after at least 1 chemotherapy and 1 NHT | Mono- or bi-allelic HRD (CDK12 excluded) | Tumor | ORR |
BRCA: 50% ATM: 7% Other HRD: 0% |
ATM: ataxia telangiectasia mutated, sBRCA: somatic deleterious mutation of BRCA. gBRCA: germinal deleterious mutation of BRCA, mCRPC metastatic castration-resistant prostate cancer, mCSPC metastatic castration-sensitive prostate cancer, nmPC non-metastatic prostate cancer, nmCSPC non-metastatic castration-sensitive prostate cancer, ADT androgen deprivation therapy, NHT new hormonal therapy, HRR homologous recombination repair, HRD homologous repair deficiency, CTID clinical trial identification, PC prostate cancer, PFS progression free survival, ORR objective response rate, PSA response rate: decline of more than 50%, RT radiotherapy
aMono- or bi-allelic status not specified
bGermline or somatic alteration specified
cComposite response rate: response according to RECIST or PSA reduction > 50%, or reduction of circulating tumor cells to less than 5/7.5 mL of blood confirmed 4 weeks later