Abstract 354P
Background
Limited data are available regarding the anticancer activity of Poly (ADP-ribose) polymerase (PARP) inhibitors in pancreatic cancer with mutations in homologous recombination repair (HRR) genes other than BRCA1/2 and PALB2.
Methods
We retrospectively reviewed the clinical characteristics and outcomes of patients with advanced pancreatic cancer harboring pathogenic germline or somatic mutation(s) in HRR gene(s) who were treated with PARP inhibitors at a single institution.
Results
A total of 48 patients were included. 36 patients had germline (g) HRR mutations (17 in gBRCA or gPALB2). 18 had somatic (s) HRR mutations (6 in sBRCA or sPALB2). 6 had both gHRR and sHRR mutations (4 had mutations in either gBRCA/PALB2 or sBRCA/PALB2). Objective response rate (ORR) was 22% in all 46 patients evaluable for response, 67% (4/6) in those with both gHRR and sHRR variants, 29% (4/14) with gBRCA/PALB2 mutations and 33% (1/3) with sBRCA/PALB2 mutations only. Median progression free survival (mPFS) and overall survival (mOS) were 6.9 and 11.5 mos. Patients with both gHRR and sHRR mutations or gHRR mutations alone had significantly longer mPFS compared to those with sHRR mutations only (10.2 vs 8.3 vs 3.0 mos, P=0.025). A similar trend was seen in mOS (11.5 vs 14.0 vs 6.8 mos, P=0.101). mPFS and mOS were 6.1 and 8.6 mos in patients with gBRCA/PALB2 mutations, 12.2 and 16.2 mos with sBRCA/PALB2 mutations, 8.3 and 17.6 mos with germline non-BRCA/non-PALB2 HRR mutations and 2.6 and 5.9 mos with somatic non-BRCA/non-PALB2 mutations only. 5 patients received olaparib as front line. There was no significant difference in ORR (20% vs 22%, P=1.000), mPFS (11.3 vs 6.9 mos, P=0.608) or mOS (11.3 vs 11.5 mos, P=0.629) compared to those who received a PARP inhibitor as maintenance.
Conclusions
Maintenance PARP inhibitor therapy can be considered in selected patients with advanced pancreatic cancer and non-BRCA/non-PALB2 HRR mutations. PARP inhibitor can be considered as first-line therapy for patients with borderline performance status harboring pathogenic alterations of BRCA1/2. Further studies are needed to verify our findings and identify biomarkers for better patient selection of PARP inhibitors in non-BRCA/non-PALB2 HRR mutant pancreatic cancer.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.