Table 2.
Clinical trials with PARP inhibitors in combination with chemotherapy in the metastatic setting.
| First Author Study Name |
Year of Study | No. of Participants (BC Patients) | Type of Study | Median/Mean No. of Prior Chemotherapy Regimens (Range) | Therapeutic Agents | Patient Population | Outcome (Objective Response Rate (ORR), Progression Free Survival (PFS)) | ||
|---|---|---|---|---|---|---|---|---|---|
| PARPi | Combination Agent | Comparative Agent/ Standard Chemotherapy |
|||||||
| Lee, J.M. et al. [57] | 2014 | 45 (8 BC) | Phase I/Ib | 5 (2–11) | Olaparib capsule, 100 mg twice daily continuous or Olaparib capsule, 200–400 mg twice daily days 1–7 |
Carboplatin AUC 3–5 every 21 days | None | gBRCAMUT | ORR in all 52.4%, ORR in breast cancer 87.5% |
| Lee, J.M. et al. [58] | 2017 | 77 (14 BC) | Phase I/Ib | 4 (1–10) |
Dose escalation: Olaparib tablet: 100–200 mg twice daily, days 1–7 300 mg twice daily maintenance after carboplatin Expansion cohort: Olaparib: Cohort A: Days 1–7 cycle 1, and days 2–8 for cycle 2; Cohort B: Days 2–8 cycle 1, and 1–7 cycle 2. Both cohorts: Days 1–7 cycle 3 up to 8; olaparib maintenance |
Dose escalation: Carboplatin AUC4–5 every 21 days, up to 8 cycles Expansion cohort: Carboplatin: Cohort A: Day 8 cycle 1, day 1 cycle 2; Cohort B: Day 1 cycle 1, day 8 cycle 2 Both cohorts: Day 1 cycle 3, up to 8 |
None | Recurrent or refractory gynecologic cancers or metastatic or inoperable breast cancer | ORR in all 46%, gBRCAMUT 68% |
| Dhawan, M.S. et al. [59] | 2017 | 24 (11 BC) | Phase I | 24% ≤ 2 lines * 12%—3 lines * 63% ≥ 4 lines* |
Talazoparib 0.75 and 1 mg daily |
Carboplatin AUC 1 and 1.5 every 2–3 weeks |
None | Advanced solid tumors | ORR in all 14% |
| Somlo, G. et al. [60] | 2017 | 77 (77 BC) | Phase I/II | Phase I: 1 (0–5) Phase II: 1 (0–5) |
Phase 1: Veliparib, 50–200 mg twice daily Phase 2: Veliparib, 400 mg twice daily and upon progression 150 mg twice daily in combination |
Phase 1: Carboplatin AUC 5/6 every 21 days Phase 2: Carboplatin AUC 5 every 21 days in combination |
None | gBRCAMUT breast cancer | Response rate in phase I, 56%; phase II—BRCA1MUT, 14%; BRCA2MUT, 36%, PFS in phase I, 8.7 months; phase II—on veliparib, 5.2 months; after combination therapy, 1.8 months |
| Appleman, L.J. et al. [61] | 2019 | 73 (16 BC) | Phase I | ≤3 lines | Veliparib 10–120 mg twice daily Days 1–7, starting cycle 2 |
Carboplatin: AUC 6 Paclitaxel: 150–200 mg/m2 Day 1 of 21-day cycle 1, Day 3 of cycle 2 onwards |
None | Advanced solid tumors | ORR in all 40%, ORR in breast cancer 69% |
| Han, H.S. et al. [62] BROCADE |
2018 | 294 (294 BC) | Phase II randomized controlled trial |
≤2 lines | Veliparib (V) 120 mg twice daily Days 1–7, 21-day cycles |
Carboplatin (C): AUC 6 Paclitaxel (P): 75 mg/m2 Day 3 |
PCP (placebo, carboplatin, paclitaxel) vs. V plus temozolomide (T) | gBRCAMUT breast cancer | ORR in VCP, 77.8%, PCP, 61.3%; VT, 28.6% PFS in VCP, 14.1 months; CP 12.3 months, V plus T, 7.4 months |
| Diéras, V. et al. [63] Arun, B.K. et al. [64] BROCADE3 |
2020 | 513 (513 BC) | Phase III Double-blinded, randomized controlled trial |
≤2 lines | Veliparib, 120 mg twice daily Days −2 to 5 If combination discontinued prior to progression, could continue with veliparib up to 400 mg twice daily |
Carboplatin (C) AUC 6 Day 1 of 21-day cycle Paclitaxel (P) 80 mg/m2 Day 1, 8, 15 of 21-day cycle |
PCP (placebo, carboplatin, paclitaxel) | gBRCAMUT HER2-negative breast cancer |
All ORR in VCP 75.8%, PCP 74.1% PFS in VCP 14.5 months, PCP 12.6 months No previous chemotherapy ORR in VCP 79.7%, PCP 76.3% PFS in VCP 16.6 months, PCP 13.1 months |
Abbreviations: BC, breast cancer. * Previous treatment regimens.