BRCA mutated pancreatic cancer: A change is coming

Table 2 Retrospective studies of platinum-chemotherapies in BRCA-mutated pancreatic ductal adenocarcinoma

Ref.	Year	Study design	Patient population	Findings
Golan et al[43]	2014	Multi-institution cohort study	71 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]	2015	Cohort study	10 patients with BRCA2 mutation and known PDAC	Duration of response on platinum agents ranged from 8-32 wk, mean of 19.3 wk
Blair et al[44]	2018	Combined case control cohort study	22 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]	2018	Cohort study	29 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]	2018	Cohort study	28 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]	2019	Case control study	32 resected PC patients with germline BRCA1, BRCA2, or PALB2 mutation, 64 resected PC patient controls without germline mutations	With 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]	2020	Case control study	26 platinum-treated patients with advanced stage PDAC and mutations of BRCA1, BRCA2 or PALB2, 52 platinum-treated, wildtype, age-matched controls	Improved 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)

HR: Homologous Repair; mOS: Median overall survival; ORR: Objective response rate; PDAC: Pancreatic adenocarcinoma; PtCh: Platinum chemotherapy; BRCA: Breast cancer susceptibility gene.