Table 1.
PARPi clinical trials with results
| PARPi monotherapy trials | Phase | Patients | Dose and schedule | Common (> 10%) adverse events | Response in BC |
|---|---|---|---|---|---|
| Olaparib [46••] Fong 2009 | I | Solid tumors (n = 60) BC (n = 9) with 3 gBRCAm carriers | Olaparib capsule 400 mg BID | G1/2: nausea, fatigue, vomiting, anemia G3/4: fatigue, thrombocytopenia | 1 CR, 1 SD 7 mo in gBRCAm, 1 PR with unknown gBRCAm status |
| Olaparib [47] Tutt 2010 | II | gBRCAm BC (n = 27) | Olaparib capsule 400 mg BID | G1/2: nausea, fatigue, vomiting G3/4: nausea, fatigue, vomiting, anemia | 0RR 41% 1 CR, 10 PR |
| Olaparib [48] Gelmon 2011 | II | OC and TNBC (n = 91) BC (n = 26); 10 gBRCAm carriers | Olaparib capsule 400 mg BID | G1/2: nausea, fatigue, vomiting, anorexia G3/4: none | 0RR0 PFS 1.8 mo PFS 3.6 mo in gBRCAm carriers |
| Olaparib [49] Kaufman 2015 | II | gBRCAm solid tumors (n = 298) gBRCAm BC (n = 62) | Olaparib capsule 400 mg BID | G1/2: nausea, fatigue, vomiting, anorexia, anemia, headache, diarrhea, dyspepsia G3/4: anemia | 0RR 12.9% SD ≥ 8 weeks 47% PFS 3.7 mo |
| Olaparib [50••] Robson 2017 | III (OlympiaD) | gBRCAm HER2 negative BC: olaparib (n = 205) vs. chemotherapy (n = 97) | Olaparib tablet300 mg BID vs. chemotherapya | G1/2: anemia, nausea, vomiting, fatigue, headache, cough G3/4: anemia | ORR 59.9% vs. 28.8% PFS 7 mo vs. 4.2 mo (p< 0.001) |
| Rucaparib [51] Drew 2016 | II | gBRCAm OC (n = 54) and BC (n = 23) | Rucaparib IV and PO (92 mg/day to 600 mg BID) | G1/2: nausea, fatigue, headache, diarrhea G3/4: none | IV - SD 44% (8/18 BC) PO - SD ≥ 12 weeks 2% (1/5 BC) |
| Talazoparib [52] Litton 2016 | II | gBRCAm BC (n = 13) | Talazoparib 1 mg/day for 2 mo followed by neoadjuvant chemotherapy | G1/2: neutropenia, anemia, nausea, fatigue G3/4: neutropenia | Tumor volume decrease in all 13 patients |
| Talazoparib [53] Turner 2017 | II | gBRCAm BC (n = 84) Cohort 1: 49 pts. after platinum based therapy Cohort 2: 35 pts. after ≥ 3 non-platinum cytotoxic regimen | Talazoparib 1 mg/day | G1/2: anemia, fatigue, nausea, diarrhea, thrombocytopenia, neutropenia G3/4: anemia, thrombocytopenia, neutropenia | Cohort 1: 21% ORR Cohort 2: 37% ORR |
| Talazoparib [54] De Bono 2017 | I | Solid tumors (n = 110) BC (n = 22) and 14pts were treated with RP2D | Talazoparib (0.025 mg-1 mg/day) | G1/2: fatigue, anemia, nausea, thrombocytopenia, alopecia, neutropenia G3/4: anemia, thrombocytopenia, neutropenia | ORR for pts. treated with RP2D: 50% (1 CR, 6 PR), 5 SD ≥ 24 weeks) All pts. had gBRCAm |
| Talazoparib [55] Litton 2017 | III (EMBRACA) | gBRCAm HER2 negative BC talazoparib (n = 287) vs. chemotherapy (n = 144) | Talazoparib 1 mg daily vs. chemotherapy | G1/2: anemia, fatigue, neutropenia, nausea, headache, thrombocytopenia G3/4: anemia, neutropenia, thrombocytopenia | ORR 62.2% vs 27.2% PFS 8.6 mo vs 5.6 mo (p < 0.001) |
| Niraparib [56] Sandhu 2013 | I | Solid tumors (n = 100) BC (n = 12), with 4 gBRCAm carriers | Niraparib 300 mg daily | G1/2: nausea, anemia, fatigue, thrombocytopenia, constipation G3/4: anemia, thrombocytopenia | 2 PR in 4 gBRCAm carriers |
| Olaparib plus Paclitaxel [57] Dent 2013 | I | TNBC (n = 19) unknown gBRCAm status | Olaparib capsules 200 mg BID and paclitaxel weekly 90 mg/m2 Olaparib maintenance 400 mg BID (Cohort 2: G-CSF prophylaxis) | G1/2: diarrhea, fatigue, nausea G3/4: neutropenia, anemia | ORR 37% |
| Olaparib capsules plus Carboplatin [58] Lee 2014 | I/Ib | gBRCAm (n = 45) with OC (n = 37) or BC (n = 8) | Olaparib capsules 400 mg BID (days 1–7) and carboplatin followed by olaparib maintenance | G1/2: nausea, fatigue, headache, GERD G3/4: neutropenia, thrombocytopenia, anemia | ORR 87.5% (1 CR, 6 PR) |
| Olaparib tablets plus Carboplatin [59] Lee 2017 | I/Ib | OC (n = 60), UT (n = 4) and BC (n = 14) - 11 TNBC, 2 hormone receptor negative HER2b and 1 hormone receptor positive/HER2b | Olaparib tablets 100–200 mg BID (days 1–7) and carboplain followed by olaparib maintenance | G1/2:anemia, thrombocytopenia, nausea, fatigue, headache G3/4:lymphopenia, thrombocytopenia, neutropenia | N/A |
| Olaparib plus Cisplatin [60] Balmana 2014 | I | Solid tumors (n = 54) BC (n = 42), with 17 gBRCAm carriers | Olaparib capsule 50–200 mg BID and cisplatin 60–75 mg/m2 followed by olaparib maintenance | G1/2: nausea, fatigue, vomiting G3/4: neutropenia, anemia, lymphopenia | ORR 71% in gBRCAm group |
| Olaparib plus AZD5363 (AKTi) [61] Michalarea 2016 | I | Solid tumors (n = 53) BC (n = 16), with 8 gBRCAm carriers | Olaparib tablets 300 mg BID and AZD 4/7 or 2/7 days | G1/2: nausea, anemia, fatigue, diarrhea, anorexia, mucositis G3/4: rash, anemia, diarrhea, vomiting, proteinuria | ORR 50% (4/8) gBRCAm and 1 sporadic TNBC |
| Rucaparib plus Cisplatin [62] Miller 2015 | II (Hoosier Oncology BRE09–146) | gBRCAm or TNBC, residual tumor post neoadjuvant anthracycline and/or taxane (n = 128) | Cisplatin 75 mg/m2 ± rucaparib IV 25–30 mg Days 1,2,3–4 cycles Rucaparib IV 30 mg or PO 100 mg weekly, 24 weeks | G1/2: nausea, neutropenia, fatigue, anorexia, anemia G3/4: neutropenia, fatigue | 2-yr DFS Cisplatin 58.3% vs. CisplatinbRucaparib 63.1% (p = 0.43) |
| Rucaparib plus Carboplatin [63] Wilson 2017 | I | Solid tumors (n = 85) BC (n = 22), with 7 gBRCAm | Rucaparib IV 12–24 mg then PO 80–360 mg and chemotherapyc | G1/2: nausea, fatigue, anemia, constipation, vomiting, diarrhea, neutropenia G3/4: thrombocytopenia, neutropenia, nausea, vomiting, anemia | 1 CR; 1 PR in gBRCAm carriers for 3 mo; and SD unknown |
| Veliparib alone, or plus Carboplatin post PD [64] Somlo 2017 | I/II | gBRCAm BC (n = 71) Phase I (n = 27), Phase II (n = 44) | Veliparib 400 mg BID (single agent); 150 mg BID (with carboplatin) | Monotherapy – G1/2: nausea, fatigue, vomiting, lymphopenia. G3/4: none G1/2: anemia, fatigue, lymphopenia, neutropenia, thrombocytopenia G3/4: thrombocytopenia, anemia, neutropenia, lymphopenia | ORR Phase I 56% Phase II14% in gBRCAlm (n = 22) and 36% in gBRCA2m (n = 22). |
| Veliparib plus Carboplatin/Paclitaxel [65] Han 2018 | II | gBRCAm BC(n = 290) | Veliparib 120 mg BID Days 1–7 or placebo, plus C/P or temozolomide | G1/2: neutropenia, thrombocytopenia, nausea G3/4: neutropenia, thrombocytopenia | PFS Veliparib 14.1 mo vs. 12.3 mo (p = 0.227) ORR Veliparib 77.8% vs. Placebo 61.3%; (p = 0.027)d |
| Veliparib plus Carboplatin/Paclitaxel [66] Rugo 2016 | II | HER2negative BC (n = 116) Veliparibb C/P (n = 72) vs. C/P (n = 44) | Veliparib 50 mg BID plus C/P | G1/2: nausea, fatigue, neutropenia, anemia, thrombocytopenia, neuropathy G3/4: neutropenia, thrombocytopenia, anemia | In TNBC, pCR Veliparibb C/P 51% vs. C/P 26% |
a
Physicians choice single-agent (capecitabine, eribulin, or vinorelbine in 21-day cycles)
b
Physicians choice single agent (capecitabine, eribulin, gemcitabine, or vinorelbine in 21-day cycle)
c
Carboplatin, paclitaxel + carboplatin, pemetrexed + cisplatin, epirubicin + cyclophosphamide
d
Arm with veliparib + temozolomide was inferior, PFS 7.4 mo and ORR 28.6%
“≥” greater than or equal
C/P carboplatin and paclitaxel, gBRCAm germline BRCA mutation, OC ovarian cancer, BC breast cancer, UT uterine cancer, ORR overall response rate, PFS progression-free survival, CR complete response, PR partial response, SD = stable disease, RP2D recommended phase 2 dose, pCR pathologic CR, G grade, mo months, yr year, BID twice daily, pt patients