Table 2.
Selected PARP inhibitor trials in BRCA 1/2-mutated (BRCAmut) ovarian cancers.
| Trial | Study population | PARP inhibitor | Comparison therapy | Clinical responsesa |
|---|---|---|---|---|
| Phase I | Advanced BRCAutmut tumors (N = 39, of which 8 BC and 23 OC) | BMN 673 | None | BRCAutmut OC |
| De Bono et al. (71) | ORR: 11/17 | |||
| NCT01286987 | ||||
| Phase I | Advanced solid tumors/hematologic malignancies (N = 100, of which 49 OC, including 22 BRCAutmut) | Niraparib | None | BRCAutmut OC |
| Sandhu et al. (68) | PR: 8/20 | |||
| NCT00749502 | ||||
| Phase I | Advanced solid tumors | Olaparib | None | BRCAutmut OC |
| Fong et al. (62) | N = 60, of which 21 OC, including 16 with BRCAutmut | PR: 8/15 | ||
| NCT00516373 | SD: 1/15 | |||
| Phase II | Recur, advanced BRCAutmut OC (N = 17)/BCs (N = 10), or BRCAtwt HGS and/or undifferentiated OC (N = 47)/TNBC (N = 16) | Olaparib | None | BRCAutmut OC |
| Gelmon et al. (65) | CR: 0/17 | |||
| NCT00679783 | PR: 7/17 | |||
| SD: 6/17 | ||||
| Phase II | Advanced PRef or PRes BRCAutmut OC | Olaparib | Liposomal doxorubicin | Olaparib 200 mg twice daily |
| Kaye et al. (66) | PFS: 6.5 months | |||
| NCT00628251 | ORR: 25% | |||
| Olaparib 400 mg twice daily | ||||
| PFS: 8.8 months | ||||
| ORR: 31% | ||||
| Liposomal doxorubicin: | ||||
| PFS: 7.1 months | ||||
| ORR: 18% | ||||
| Phase II | BRCAutmut solid tumors (BC, N = 62, OC, N = 193) | Olaparib | None | BRCAutmut OC |
| Kaufman et al. (89) | CR: 6/193 | |||
| NCT01078662 | PR: 54/193 | |||
| SD: 78/193 | ||||
| PFS rate: 54.6% for 6 months | ||||
| OS rate: 64.4% for 12 months | ||||
| Phase II | Advanced BRCAutmut OC | Olaparib | None | ORR: 11/33 |
| Audeh et al. (63) | CR: 2/33 | |||
| NCT00494442 | PR: 9/33 | |||
| PFS: 5.8 months | ||||
| Phase I | Met or unresect BRCAutmut BC and EOC (N = 45, of which 37 OC) | Olaparib + carboplatin | None | BRCAutmut OC |
| Lee et al. (72) | CR: 0/34 | |||
| NCT00647062, NCT01445418 | PR: 15/34 | |||
| SD: 14/34 | ||||
| Phase I | Advanced solid tumors N = 87, including BC (26%) and OC (7%), of which 12 BRCAutmut | Olaparib + carboplatin ± paclitaxel | None | BRCAutmut |
| van der Noll et al. (90) | CR: 17%b | |||
| NCT00516724 | PR: 33%b | |||
| Phase I | Recur or advanced EOC/TNBC | Olaparib + cediranib (angiogenesis inhibitor) | None | BRCAutmut OC |
| Liu et al. (82) | N = 28, of which 12 BRCAutmut OC | CR: 1/11 | ||
| NCT01116648 | PR: 4/11 | |||
| Phase I/II Kristeleit et al. (69) NCT01482715 | Advanced solid tumors and relapsed PSens BRCAutmut OC | Rucaparib | None | BRCAutmut OC PR: 1/7 |
| N = 29, of which 17 BC and 7 OC, including BRCAutmut tumors | SD: 10/29 (of which 5 were OC, also 7 were BRCAutmut)b | |||
| CR + PR + SD: 6/7 in OC | ||||
| Phase I | Advanced BRCAutmut solid tumors (N = 38, of which 20 OC), or BRCAtwt BLBC or OC | Veliparib | None | BRCAutmut OC |
| Huggins-Puhalla et al. (91) | PR: 1/20 | |||
| NCT00892736 | SD: 10/38b | |||
| Phase II Kummar et al. (97) NCT01306032 | Refractory progressive BRCAutmut OC or HGS OC | Veliparib (V) + cyclophosphamide (C) | Cyclophosphamide (C) | V + C: PR: 3/36b C: PR: 5/38b |
| N = 36 | N = 38 | |||
| Phase I | Met or unresect solid tumors | Veliparib + carboplatin and gemcitabine | None | CR: 2/59b |
| Bell-McGuinn et al. (98) | N = 59, of which 39 OC, 24 of 39 OC BRCAutmut | PR: 11/59b | ||
| NCT01063816 | Of 13 responses, 8 BRCAutmut OC, 3 other OC |
aData include only patients with measurable disease.
bCollective data reported.
BC, breast cancer; OC, ovarian cancer; ORR, objective response rate; PR, partial response; SD, stable disease; recur, recurrent; BRCAwt, BRCA-wild type; HGS, high-grade serous; TNBC, triple negative breast cancer; PRef, platinum-refractory; PRes, platinum-resistant; PFS, progression free survival; OS, overall survival; CR, complete response; met, metastatic; unresect, unresectable; EOC, epithelial ovarian cancer; PSens, platinum-sensitive; BLBC, basal-like breast cancer.