Table 1.
Poly (ADP-Ribose) Polymerase Inhibitor Studies in Pancreatic Cancer
| Agent | Patient population | Biomarkers | Study type | Combination | Results (ORR, DCR, PFS, OS, or SD) | Ref |
|---|---|---|---|---|---|---|
| Olaparib | Recurrent cancer (breast, ovarian, pancreatic, or prostate) | gBRCA1/2 mutation | II | No | ORR 26% and 21.7% in patients with pancreatic cancer. | 27 |
| Veliparib | 16 patients, 5 (31%) BRCA1, 11 (69%) BRCA2 gm. 14 (88%) received prior platinum-based therapy | gBRCA1/2, PALB2 mutation | II | No | PRs (6%) PD (25%) SD 11 (69%) PD as: median PFS 1.7 months, median OS 3.1 months (95% CI 1.9–4.1) |
28 |
| Olaparib | POLO study, 144 participants sensitive to platinum agents | gBRCA1/2 mutations | III | No | Improved Pfs (7.4 months olaparib vs. 3.8 months placebo). | 30 |
| ABT-888 (Veliparib) | SWOG S1513 trial mFOLFIRI+veliparib vs. FOLFIRI in second-line setting 143 participants, standard eligibility study |
Germ line/somatic BRCA1/2 mutations, and other DDR markers as correlates not necessary for enrolling | II | mFOLFIRI | Permanently closed before reach it end-point | 41 |
| Rucaparib | RUCAPANC trial: 19 BRCA+ relapsed mPAC pts |
gBRCA1/2 mutation | II | N/A | ORR was 11% (1 PR, and 1 CR); DCR ≥12 weeks was 32% | 29 |
| Veliparib | 52 pts with BRCA+/PLAP2+ | BRCA1/2 mutation | I | Gemcitabine and cisplatin | 52 pts with BRCA+/PLAP2+. Median OS 15.5 months triplet vs. 16.4 doublet | 43 |
| Olaparib | 66 patients, nonselected for biomarkers | N/A | I | Gemcitabine 600 mg/m2 | No significant difference | 64 |
| Olaparib | Pre-clinical, in vitro xenografts, 96 PC cells. Goal to assess ability of combination Chk1-PARP1 inhibition to sensitize to radiation therapy | N/A | I | Chk1 inhibitor AZD7762 | AZD7762+olaparib is a significant radiosensitization in p53 mutant MPC | 65 |
CR, complete response; DCR, disease control rate; DDR, DNA damage repair defect; MPC, metastatic pancreatic cancer; ORR, objective response rate; OS, overall survival; PARP, poly (ADP-ribose) polymerase; PFS, progression-free survival; PR, partial response; SD, stable disease.