Retrospective Survival Analysis of Patients With Advanced Pancreatic Ductal Adenocarcinoma and Germline or Mutations.

PURPOSE

Germline mutations in the homologous recombination (HR) genes , , and confer an increased risk for pancreatic ductal adenocarcinoma (PDAC). Tumors associated with mutations in HR genes are sensitive to DNA-damaging agents, such as platinum chemotherapies. We hypothesized that patients with PDAC with germline , , or mutations may benefit preferentially from platinum-based chemotherapy.

MATERIALS AND METHODS

Twenty-nine individuals with deleterious germline mutations in , , or and a diagnosis of advanced PDAC (mut-positive) were matched 2:1 to patients who were noncarrier or untested (control) by age at diagnosis, year of diagnosis, stage, and sex. Patients were identified via one of two available databases at the University of Pennsylvania: the Basser Center for BRCA Registry or the University of Pennsylvania Electronic Medical Patient Record. Treatment history, including exposure to platinum-based chemotherapy, was ascertained. Primary objective was overall survival (OS).

RESULTS

Patients who were mut-positive had an OS of 21.8 months; control patients had an OS of 8.1 months (hazard ratio [HR], 0.35; 95% CI, 0.2 to 0.62;  < .001). With platinum exposure, patients who were mut-positive had an undefined OS (median follow-up, 20.1 months), versus an OS of 15.5 months in the control patients (HR, 0.25; 95% CI, 0.1 to 0.61; = .002). In patients not treated with platinum, there was no significant difference in OS between groups (HR, 0.54; 95% CI, 0.25 to 1.17; = .12). When treated with platinum therapy, patients who were mut-positive had a 1-year OS of 94%, compared with a 1-year OS of 60% in control patients.

CONCLUSION

Platinum-based therapy may confer a survival benefit in patients with advanced PDAC who carry a deleterious germline , , or mutation.