Emerging strategies in BRCA-positive pancreatic cancer

Abstract

Purpose: We propose a treatment algorithm for PDAC with particular emphasis on BRCA1 or 2 mutation-positive patients. Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest diseases in the United States and Europe. BRCA1 and BRCA2 are among the most common of the known genetic mutations involved in familial PDAC. The optimal chemotherapy regimen to use for BRCA1 or 2 mutation carriers with PDAC is not yet established. As new treatment options emerge, algorithms must balance the need to give the best drugs first with ensuring that there are still beneficial options available for later. Methods: We conducted a review of the literature for data on possible therapies in BRCA-positive and BRCA-negative pancreatic cancer. Results: There is accumulating evidence of increased sensitivity to platinum-based therapy and poly-ADP-ribose polymerase inhibitors (PARPi) in BRCA-associated PDAC. There are no studies relating to borderline BRCA-associated PDAC and, therefore, same treatment as for sporadic PDAC seems appropriate. Treatment of unresectable PDAC varies depending on stage of the disease. Patients with BRCA-associated locally advanced PDAC can benefit from targeted therapy with PARPi (olaparib) as a second-line therapy after antimetabolite treatment failure. Patients with unresectable metastatic BRCA-positive PDAC may benefit from platinum-based therapy. Conclusion: Targeted therapies are shifting the treatment paradigms and increasing survival for patients with PDAC, a group that used to have a grim prognosis.