Table 1:
Selected Completed PARPi Trials in Pancreas Cancer
| Drugs | N | Phase | Cohort | Study design | Outcome | Reference |
|---|---|---|---|---|---|---|
| Olaparib | 154 | 2 | gBRCA1/BRCA2 mutation and had not progressed during first line platinum | Olaparib 200mg bid vs placebo | mPFS 7.4 vs 3.8 mos (HR 0.53; 95% CI, 0.35 to 0.82; P=0.004) mOS 19.0 vs 19.2 mos (HR 0.83 favoring olaparib; 95% CI 0.56–1.22; P= 0.3487. |
Golan et al[78,66] |
| Rucaparib | 24 | 2 | Platinum sensitive PDAC with BRCA1/BRCA2 or PALB2 mutations | Rucaparib 600mg bid | ORR 36.8% DCR for >8 weeks 89.5% mPFS 9.1 mos (no HR given) |
Binder et al[81] |
| Olaparib | 23 | 2 | gBRCA1/2 solid tumors | Olaparib 400mg bid | RR 21.7% SD 34.8% |
Kaufman et al[82] |
| Rucaparib | 19 | 2 | gBRCA1/2 and somatic BRCA1/2 | Rucaparib 600mg bid | ORR 15.9% DCR 31.6% or 44.4% in those with prior chemotherapy |
Shroff et al[83] |
| Veliparib | 16 | 2 | gBRCA1/2, PALB2 mutated PDAC | Veliparib 300 mg bid n=3), 400 mg bid (n=15) | RR 0% SD 25% mPFS 1.7mos (95% CI 1.57–1.83) mOS 3.1mos ((95% CI 1.9–4.1) |
Lowery et al[84] |
| Olaparib | 48 | 2 | Platinum-sensitive, metastatic PDAC, without gBRCA mutation and with BRCAness, previous chemotherapy | Olaparib 400mg bid | (n=46) RR 2% SD 72% mPFS 3.7mos (95% CI, 2.9–5.7) mOS 9.9mos (95% CI, 7.6–16.1 months) |
Javle et al[68] |
| Olaparib | 18 | 1 | Unresectable PDAC | MTD of olaparib and irinotecan, cisplatin, mitomycin C | Significant toxicity One 4-year response in germline BRCA mutated patient |
Yarchoan et al[86] |
| Veliparib | 108 | 2 | Metastatic PDAC | Veliparib plus modified FOLFIRI (no 5FU bolus) vs FOLFIRI alone | mOS was 5.1 vs 5.9 mos (HR 1.3, 95%CI 0.9–2.0, P = 0.21), and mPFS was 2.1 vs 2.9 mos (HR 1.5, 95%CI 1.0–2.2, P = 0.05) | Chiorean et al[87] |
| Veliparib | 31 | 1/2 | Metastatic PDAC | Veliparib (40 mg to 250 mg twice a day, days 1–7 of each 14-day cycle) and FOLFOX vs FOLFOX alone | ORR in HRR mutated platinum naïve patients of 57% | Pishvaian et al[89] |
| Veliparib | 50 | 2 | Stage 3/ 4 PDAC with gBRCA/PALB2 mutation | Veliparib 80mg bid 1–12 cycled every 3 weeks plus cisplatin and gemcitabine vs cisplatin and gemcitabine alone | RR 74.1% DCR 100% mPFS 10.1 (95% CI, 6.7 to 11.5 months) vs 9.7 (95% CI, 4.2 to 13.6 months; P = .73) mOS 15.5 (95% CI, 12.2 to 24.3 months) vs 16.4 (95% CI, 11.7 to 23.4 months; P = .6) |
O’Reilly et al[90] |
| Veliparib | 30 | 2 | Locally advanced PDAC | Veliparib 40mg bid, weekly gemcitabine, daily IMRT | OS for DDR mutated patients 19 mos 95% CI: 6.2–27.2 vs 14mos in DDR intact patients. | Tuli et al[121] |
RR: Response rate; SD: Stable disease; POD: Progression of disease; BID: twice daily, mPFS: Median progression free survival, mOS: Median overall survival; gBRCA: germline BRCA mutated, mos: months; wks: weeks); MTD Maximum tolerated dose; IMRT: Intensity modulated radiotherapy