PARP Inhibitors in Pancreatic Cancer with Homologous Recombination Repair Gene Mutations: A Single-Institution Experience.

Background: Limited data are available regarding the anticancer activity of PARP inhibitors (PARPis) in pancreatic cancer with mutations in HRR genes other than and .

Methods: We retrospectively reviewed the clinical characteristics and outcomes of 48 patients with advanced pancreatic cancer harboring pathogenic germline and/or somatic HRR mutations who were treated with PARPis.

Results: Thirty patients had germline (g)HRR mutations only, twelve had somatic (s)HRR mutations only, and six had concomitant gHRR and sHRR mutations. The objective response rate (ORR) was 22%. The median progression-free survival (mPFS) and overall survival (mOS) were 6.9 and 11.5 months, respectively. Five patients received olaparib in the front-line setting due to borderline performance status. Their ORR was 20%, and their mPFS and mOS were both 11.3 months. The ORR was higher in patients with or mutations (germline or somatic) than in those with non-/ mutations. Patients with somatic non-/ variants had a shorter mPFS. Patients with concomitant gHRR/sHRR mutations or gHRR mutations alone had a significantly longer mPFS than those with sHRR mutations only.

Conclusions: PARP inhibitors may be considered for patients with advanced pancreatic cancer harboring pathogenic alterations of who cannot tolerate standard chemotherapy. Maintenance PARPis can be considered in selected patients with non-/non- HRR mutations.