Copyright ©The Author(s) 2021.
World J Gastroenterol. May 7, 2021; 27(17): 1943-1958
Published online May 7, 2021. doi: 10.3748/wjg.v27.i17.1943
Table 1 Summary of studies of incidence of germline BRCA mutations in unselected pancreatic cancer cohorts
Cohort size (Number AJ)
Germline BRCA1 pathogenic mutation incidence (%)
Germline BRCA2 pathogenic mutation incidence (%)
Combined germline BRCA mutation Incidence
Holter et al[23]2015North American306 (33)1.0%3.6%4.6%
Brand et al[24]2018North American298 (26)1.3%1.3%2.6%
Mizukami et al[25]2020Japanese1005 (-)1.7%2.5%4.2%
Grant et al[6]2015North American290 (13)0.3%0.7%1%
Lowery et al[26]2018North American615 (111)2.3%5.7%8%
Table 2 Retrospective studies of platinum-chemotherapies in BRCA-mutated pancreatic ductal adenocarcinoma
Study design
Patient population
Golan et al[43]2014Multi-institution cohort study71 patients with germline BRCA mutations (21 BRCA1, 49 BRCA2, 1 both)Superior mOS in stage 3/4 patients treated with platinum compared to non-platinum chemotherapy (22 vs 9 mo, P = 0.039)
Vyas et al[51]2015Cohort study10 patients with BRCA2 mutation and known PDACDuration of response on platinum agents ranged from 8-32 wk, mean of 19.3 wk
Blair et al[44]2018Combined case control cohort study22 patients with resected sporadic PDAC and germline BRCA mutations (1 BRCA1, 18 BRCA2)Improved OS in BRCA-mutated patients treated with adjuvant PtCh compared to patients treated with alternative chemotherapies or no adjuvant therapy (31.0 vs 17.8 vs 9.3 mo, P < 0.001)
Reiss et al[52]2018Cohort study29 patients with unresectable PDAC and germline mutations of BRCA1, BRCA2 or PALB2(12 BRCA1, 15 BRCA2, 2 PALB2)Superior mOS in platinum-treated patients (undefined mOS (median follow up 21 mo) vs 15.5 mo, P = 0.02)
Kondo et al[35]2018Cohort study28 patients with advanced PDAC (13 had HR-related gene mutations, 15 without mutations to HR-related genes)Superior median PFS in HR-mutated PDAC patients treated with platinum chemotherapy compared to PDAC patients without HR mutations treated with platinum therapy (20.8 mo vs 1.7 mo, P = 0.049)
Yu et al[54]2019Case control study32 resected PC patients with germline BRCA1, BRCA2, or PALB2 mutation, 64 resected PC patient controls without germline mutationsWith peri-operative platinum exposure, mOS was longer in mutation-positive group that mutation negative group (mOS not yet met vs 23.1 mo, HR= 0.12)
Wattenberg et al[53]2020Case control study26 platinum-treated patients with advanced stage PDAC and mutations of BRCA1, BRCA2 or PALB2, 52 platinum-treated, wildtype, age-matched controlsImproved ORR in patients with mutations compared to controls (58% vs 21%, P = 0.0022). Improved real world PFS in mutation carriers (10.1 mo vs 6.9 mo, HR = 0.43, P = 0.0068)
Table 3 Ongoing phase II clinical trials investigating poly (ADP-ribose) polymerase inhibitor/Immune Checkpoint blockade combination therapy in pancreatic ductal adenocarcinoma
Study identifier
Patient population
PARP inhibitor
Phase and design
Estimated completion date
NCT03404960Advanced PDAC patients who did not progress on PtChNivolumab or IpilimumabNiraparibPhase Ib/II trial evaluating effectiveness of olaparib with either nivolumab or ipilimumabJune 2021
NCT03851614Advanced PDAC, leiomyosarcoma or mismatch repair-proficient colorectal cancerDurvalumabOlaparibPhase II trial evaluating impact of combination therapy on genomic and immune biomarkersMarch 2022
NCT04493060Metastatic PDAC with mutations of BRCA1/2 or PALB2, previously treated with 1-2 lines of chemotherapy including a PtCh agentDostarlimabNiraparibPhase II, evaluating the disease control rate at 12 weeks (DCR12) with combination therapy December 2022
NCT04548752Metastatic PDAC with germline BRCA1 or BRCA2 mutation treated with first-line PtChPembrolizumabOlaparibPhase II trial comparing combination therapy to olaparib alone as maintenance therapyMarch 2025