Table 3 Phase 1/2 studies of PARPi as combination therapy in metastatic breast cancers, with spotlight on BRCA mutated patients
From: PARP inhibitors in the management of breast cancer: current data and future prospects
Study name (NCT) | Ref. | Phase | Tumor type | No. of patients | Investigation arm | Primary endpoint | Overall results | Results in BRCAm BC | Additional notes |
|---|---|---|---|---|---|---|---|---|---|
[total/BC (BRCAm BC)] | |||||||||
Olaparib | |||||||||
NCT00707707 | [122] | 1 | TNBC | 19/19 (NK) | Olaparib (200 mg bid) + PTX (90 mg/m2) | Safety and tolerability | ORR: 37 % | – | First- or second-line treatment only |
NCT00710268 | [79] | 1 | Solid tumors | 12/3 (NK) | Olaparib (100–400 mg bid) + BEV (10 mg/kg) | Safety and tolerability | No data on response reported | – | No grade 3 or 4 hematologic toxicities |
NCT00782574 | [23] | 1 | BC, OC, peritoneal cancer, pancreatic cancer | 54/42 (17) | Olaparib (50–200 mg bid continuously vs. intermittent) + CDDP (75 mg/m2) | Safety and tolerability | ORR: 41 % | ORR: 71 % | Continuous olaparib schedules not tolerable (hematologic toxicity) |
NCT01116648 | [45] | 1 | TNBC, OC | 28/8 (3) | Olaparib (100–400 mg bid) + cediranib (20–30 mg) | Safety and tolerability | Overall ORR: 29 % | ORR: 0 % |  |
BC ORR: 0 % | |||||||||
BC CBR: 29 % | |||||||||
NCT01445418 | [123] | 1 | BRCAm OC and BC | 45/8 (8) | Olaparib (100–400 mg bid) + CBDCA (AUC 3–5) | Safety and tolerability | ORR: 52 % | ORR: 88 % | One CR in BRCAm BC for 3 months |
Veliparib | |||||||||
NCT00535119 | [124] | 1 | Solid tumors | 68/14 (NK) | Veliparib (20–120 mg) + CBDCA (AUC 5–6) + PTX (150–200 mg/m2) | PK, safety and tolerability | ORR: 19 % | – | One CR in BC |
NCT00740805 | [125] | 1 | Solid and hematologic tumors | 18/14 (5) | Veliparib (50–150 mg) + DOX (60 mg/m2) + CYC (600 mg/m2) | Tolerability | No overall results reported | ORR: 60 % | Expansion cohort study in BC ongoing |
NCT01063816 | [126] | 1 | Solid tumors | 59/10 (NK) | Veliparib (250 mg bid) + CBDCA (AUC 4) + GEM (800 mg/m2) | PK, safety and tolerability | ORR: 22 % | – |  |
NCT01104259 | [53] | 1 | TNBC or BRCAm BC | 45/45 (12) | Veliparib (20–300 mg) + CDDP (75 mg/m2) + VNR (25 mg/m2) | Tolerability | ORR: 55 % | ORR: 73 % |  |
NCT01251874 | [127] | 1 | BC | 44/44 (16) | Veliparib (50–200 mg) + CBDCA (AUC 5–6) | Safety and tolerability | ORR: 19 % | ORR: 25 % |  |
NCT01445522 | [128] | 1 | Solid tumors and lymphomas | 35/12 (NK) | Veliparib (20–80 mg) + CYC (50 mg) | Safety and tolerability | ORR: 20 % | – |  |
Not reported | [54] | 1 | BRCAm BC | 26/26 (26) | Veliparib (50–200 mg) + CBDCA (AUC 5–6) | Safety and tolerability | – | ORR: 46 % |  |
CBF: 74 % | |||||||||
NCT01281150 | [55] | 1 | Solid tumors | 30/24 (5) | Veliparib (50–200 mg) + PTX (80 mg/m2) + CBDCA (AUC 5–6) | Tolerability | ORR: 48 % | ORR: 60 % | ORR in non-mutated BRCA BC: 67 % |
NCT01009788 | [52] | 2 | BC | 41/41 (8) | Veliparib (40 mg bid) + TMZ (150 mg/m2) | ORR | ORR: 13 % | ORR: 50 % | Expansion cohort with additional 20 patients with BRCA1/2 mutations: ORR 15 %, CBR: 45 % |
CBF: 63 % | |||||||||
Rucaparib | |||||||||
NCT01009190 | [129] | 1 | Solid tumors | 23/5 (NK) | Rucaparib (80–360 mg) + CBDCA (AUC 3–5) | Safety and tolerability | DCR: 50 % | – |  |
CEP-9722 | |||||||||
NCT00920595 | [130] | 1 | Solid tumors | 26/7 (NK) | CEP-9722 (150–1000 mg) + TMZ (150 mg/m2) | PK, PD, safety and anti-tumor activity | ORR: 5 % | – |  |