Table 2.
Clinical trials of PARP inhibitors including ovarian cancer patients.
| Study (year) | Study population | Phase | Treatment | Patients (n) | RR (%)† | CBR (%) | PFS or RD | Toxicity | Ref. |
|---|---|---|---|---|---|---|---|---|---|
| Fong et al. (2009) | Refractory solid tumors (OC, breast, colorectal, melanoma, sarcoma and others) | I | Olaparib: dose escalation and expansion at 600 mg twice daily | 60 (OC: 21) | 53 | 60 | – | Grade 1 or 2 | [93] |
| Audeh et al. (2010) | BRCA-associated recurrent advanced OC | II | Olaparib: 400 mg twice daily and 100 mg twice daily | 57 | 400 mg dose: RECIST, 33; RECIST/GCIG, 61; 100 mg dose: RECIST, 13; RECIST/GCIG, 17 | 400 mg dose: 66; 100 mg dose: 42 | PFS (months): olaparib 400 mg dose, 5.8; 100 mg dose, 1.9 | Mainly grade ≤2 | [94] |
| Fong et al. (2010) | BRCA-associated OC that progressed after platinum agent | II | Olaparib: dose escalation and expansion at 200 mg twice daily | 50 | RECIST/GCIG, 40 | Overall: 46; platinum sensitive: 69; platinum resistant: 46; platinum refractory: 23 (p < 0.05) | RD of all responding patients (weeks): 28 | Mainly grade ≤2 | [95] |
| Gelmon et al. (2011) | Advanced high-grade serous undifferentiated OC; triple-negative breast cancer | II | Olaparib: 400 mg twice daily | 91 (OC: 65) | Total: 29; BRCA1/2 mutations: 41; non-BRCA: 24 | Total: 67; BRCA1/2 mutations: 76; non-BRCA: 63 | PFS (days): total, 219; BRCA1/2 mutations, 221; non-BRCA, 192 | 36% grade ≥3 | [96] |
| Kaye et al. (2012) | Recurred within 12 months of prior platinum treatment; BRCA1/2-mutated OC | II | Olaparib: 400 mg or 200 mg twice daily, or PLD 50 mg/m2 every 28 days | 97 | Olaparib 400 mg: RECIST, 31; RECIST/GCIG, 59 200 mg: RECIST, 25; RECIST/GCIG, 38 PLD: RECIST, 18; RECIST/GCIG, 39 |
Olaparib 400 mg: 59 200 mg: 47 PLD: 52 |
PFS (months): olaparib 400 mg, 8.8; 200 mg, 6.5; PLD 50 mg/m2, 7.1 | Generally grade ≤2 | [97] |
| Ledermann et al. (2012) | Platinum-sensitive, relapsed, high-grade serous OC | II | Olaparib 400 mg twice daily or placebo | 265 | Olaparib 12; Placebo 4 | Olaparib: 53; placebo: 25 | PFS (months): olaparib, 8.4; placebo, 4.8 | Most grade 1 or 2 | [98] |
†
RR according to RECIST criteria unless stated otherwise.
CBR: Clinical benefit rate (response rate + stable disease); GCIG: Gynecologic Cancer Intergroup; OC: Ovarian cancer; PFS: Progression-free survival; PLD: Pegylated liposomal doxorubicin; RD: Response duration; RECIST: Response Evaluation Criteria In Solid Tumors; RR: Response rate (complete + partial responses).