Audeh MW et al. Lancet. 2010 [4].
|
Recurrent epithelial ovarian, primary peritoneal, or fallopian tube carcinoma
|
BRCA1/2 positive
|
Cohort 1: Olaparib 400 mg BID
Cohort 2: Olaparib 100 mg BID
|
57
|
ORR
|
Cohort 1: 33%
Cohort 2: 13%
|
Cohort 1: 5.8 months
Cohort 2: 1.9 months
|
Positive proof of concept of utility of PARP inhibitors from phase I data. Superior efficacy of 400 mg BID dosing.
|
Kaye SB et al. J Clin Oncol. 2012 [73].
|
Platinum resistent recurrent epithelial ovarian, primary peritoneal, or fallopian tube carcinoma
|
BRCA1/2 positive
|
Arm 1: Olaparib 200 mg BID
Arm 2: Olaparib 400 mg BID
Arm 3: PLD 50 mg/m2
|
97
|
PFS
|
Arm 1: 25%
Arm 2: 31%
Arm 3: 18%
|
Arm 1: 6.5 months
Arm 2: 8.8 months
Arm 3: 7.1 months
|
No significant difference in outcomes between 2 doses of olaparib and PLD.
|
Gelmon KA et al. Lancet Oncol. 2011 [57].
|
Advanced metastatic or recurrent ovarian, primary peritoneal or fallopian tube cancer (high-grade serous and/or undifferentiated) or breast cancer
|
BRCA1/2 positive AND
BRCA1/2 negative
|
Olaparib 400 mg BID
|
91 (65 with gynecologic cancer)
|
ORR
|
BRCA1/2 positive: 41%
BRCA1/2 negative: 24%
BRCA1/2 positive + platinum sensitive: 60%
BRCA1/2 negative + platinum sensitive: 50%
BRCA1/2 positive + platinum resistant: 33%
BRCA1/2 negative + platinum resistant: 4%
|
BRCA1/2 positive: 221 days
BRCA1/2 negative: 192 days
|
Olaparib has activity in BRCA1/2 positive and negative populations.
|
Ledermann J et al. Lancet Oncol. 2014 [5].
|
Platinum sensitive recurrent high grade serous epithelial ovarian, primary peritoneal, or fallopian tube carcinoma
|
BRCA1/2 positive AND
BRCA1/2 negative
|
(Maintenance therapy following platinum-based chemotherapy)
Arm 1: Olaparib 400 mg BID
Arm 2: Placebo
|
265
|
PFS
| |
Arm 1: 8.4 months
Arm 2: 4.8 months
Olaparib + BRCA1/2 positive: 11.2 months
Olaparib + BRCA1/2 negative: 5.6 months
Placebo + BRCA1/2 positive: 4.3 months
Placebo + BRCA1/2 negative: 5.5 months
|
Olaparib maintenance associated with improved PFS. No diffrence in OS.
|
Oza AM et al. Lancet Oncol. 2015 [74].
|
Platinum sensitive recurrent serous ovarian cancer
|
BRCA1/2 positive AND
BRCA1/2 negative
|
Arm 1: Olaparib 200 mg BID + Paclitaxel 175 mg/m2 + Carboplatin AUC 4 × 6 cycles followed by olaparib 400 mg BID maintenance
Arm 2: Paclitaxel 175 mg/m2 + Carboplatin AUC 4 × 6 cycles
|
162
|
PFS
|
Arm 1: 64%
Arm 2: 58%
|
Arm 1: 12.2 months
Arm 2: 9.6 months
|
Olaparib associated with improved PFS.
|
Coleman RL et al. Gynecol Oncol. 2015 [75].
|
Recurrent or persistent ovarian, primary peritoneal or fallopian tube cancer
|
BRCA1/2 positive
|
Veliparib 400 mg BID
|
52
|
ORR
|
Total population – 26%
Platinum resistant – 20%
Platinum sensitive – 35%
BRCA1 – 26%
BRCA2 – 27%
|
8.11 months
|
Veliparib has single agent acitivity in platinum resistent disease.
|
Kaufman B et al. J Clin Oncol. 2015 [76].
|
Platinum resistent recurrent ovarian, primary peritoneal or fallopian tube cancer
|
BRCA1/2 positive
|
Olaparib 400 mg BID
|
193
|
ORR
|
31%
|
225 days
|
Olaparib has single agent acitivity in BRCA1/2 positive platinum resistent disease.
|
Kummar S et al. Clin Cancer Res 2015 [58].
|
Recurrent ovarian cancer or recurrent primary peritoneal, fallopian tube or high-grade serous ovarian cancers
|
BRCA1/2 positive AND
BRCA1/2 negative
|
Arm 1: Cyclophosphamide 50 mg daily
Arm 2: Cyclophosphamide 50 mg daily + Veliparib 60 mg daily
|
75
|
ORR
|
Arm 1: (n = 38) 1 complete response, 6 partial responses
Arm 2: (n = 37) 1 complete response, 3 partial responses
|
Arm 1: 2.3 months
Arm 2: 2.1 months
|
The addition of veliparib to cyclophosphamide did not improve the response rate or the median PFS.
|
Mirza MR et al. N Engl J Med 2016 [48].
|
Platinum sensitive recurrent ovarian cancer or recurrent primary peritoneal, fallopian tube or high-grade serous ovarian cancers
|
BRCA1/2 positive AND
BRCA1/2 negative
|
Niraparib 300 mg daily vs. placebo daily
|
553
|
PFS
| |
gBRCA cohort
- Niraparib: 21.0 months
- Placebo: 5.5 months
non-gBRCA with HRD cohort
- Niraparib: 12.9 months
- Placebo: 3.8 months non-gBRCA cohort - Niraparib: 9.3 months - Placebo: 3.9 months
|
Niraparib maintenance therapy has activity for platinum-sensitive recurrent ovaruan cancer regardles of the presence or absense of gBRCA mutations or HRD status.
|
Swisher EM, et al. Lancet Oncol 2017 [59].
|
Platinum sensitive recurrent ovarian cancer or recurrent primary peritoneal, fallopian tube or high-grade ovarian cancers
|
BRCA1/2 positive AND
BRCA1/2 negative
|
Rucaparib 600 mg BID
|
206
|
PFS
|
BRCA 1/2 positive – 80%
BRCA1/2 wild-type and LOH high – 29%
BRCA1/2 wild-type and LOH low – 10%
|
BRCA 1/2 positive: 12.8 months
BRCA1/2 wild-type and LOH high: 5.7 months
BRCA1/2 wild-type and LOH low: 5.2 months
|
Rucaparib acitivity in BRCA1/2 mutant and BRCA wild-type LOH high platinum sensitive recurrent disease.
|