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Table 3 Phase II/III studies of PARP inhibitors in ovarian cancer

From: Homologous recombination deficiency (HRD) testing in ovarian cancer clinical practice: a review of the literature

Study Patient population BRCA status of patient population Treatment arms Total accrual Primary endpoint Results
Objective Response Rate (ORR) Progression free survival (PFS) Pertinent Findings
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.
  1. gBRCA Germline BRCA mutation, non-gBRCA Non-germline BRCA mutation, LOH Loss of heterozygosity