Retrospective Survival Analysis of Patients With Resected Pancreatic Ductal Adenocarcinoma and a Germline or Mutation.

Purpose: Germline mutations in the homologous recombination genes , , and confer an increased risk for pancreatic ductal adenocarcinoma (PDAC). Tumors associated with mutations in homologous recombination genes are sensitive to DNA-damaging agents. We retrospectively studied patients with resected PDAC and a pathogenic germline mutation in one of these three genes. The planned analyses included overall survival (OS) and changes therein when platinum chemotherapy was used in the perioperative setting.

Materials And Methods: Thirty-two individuals with pathogenic germline mutations in , , or and resected PDAC (mutation positive) were matched in a 1:2 fashion to patients who were noncarriers or untested (mutation negative) by age, year of diagnosis, stage, and sex. Patients were identified via one of two available databases at University of Pennsylvania: the Basser Center for BRCA Registry or the electronic medical record. The primary outcome was OS.

Results: Patients in the mutation-positive group had a median OS (mOS) of 46.6 months; those in the mutation-negative group had an mOS of 23.2 months (hazard ratio [HR], 0.49; 95% CI, 0.27 to 0.88). With platinum exposure in the perioperative setting, mOS in the mutation-positive group had not yet been met versus a mOS of 23.1 months in the mutation-negative group (HR, 0.12; 95% CI, 0.01 to 1.00). When neither group was treated with platinum, there was no significant OS difference between groups (HR, 0.52; 95% CI 0.12 to 2.24). Patients in the mutation-positive group who received perioperative treatment with platinum had a trend toward improved mOS compared with those who did not (HR, 0.15; 95% CI, 0.02 to 1.23; = .07).

Conclusion: Platinum-based chemotherapy may confer a survival benefit in patients with resected PDAC and a pathogenic germline , , or mutation. Knowledge of a germline mutation may be important to determine best choice of perioperative chemotherapy.