Dr Bekaii-Saab on Frontline Treatment Considerations for BRCA1/2+ Pancreatic Cancer

Tanios Bekaii-Saab, MD, FACP, professor, medicine, Mayo Clinic College of Medicine and Science; leader, Gastrointestinal Cancer Program, Mayo Clinic Comprehensive Cancer Center; medical director, Cancer Clinical Research Office; vice chair, section chief, Medical Oncology, Department of Internal Medicine, Mayo Clinic, discusses the evolving treatment paradigm for patients with BRCA1- and BRCA2-positive pancreatic cancer in the first-line setting.

For most patients with pancreatic cancer treatment options are limited to cytotoxic chemotherapy regimens, such as FOLFIRINOX or gemcitabine plus nab-paclitaxel (Abraxane). However, in patients with microsatellite instability–high (MSI-H) tumors, which represent only about 0.5% of pancreatic cancer cases, immune checkpoint inhibitors like pembrolizumab (Keytruda) are favored as first-line therapy.

Saab explains that the presence of BRCA1/2 mutations, whether germline (2% to 3%) or somatic (about 2%), further guides treatment choices. In the subset of patients who are BRCA1/2 positive, platinum-based chemotherapy regimens are preferred due to their demonstrated efficacy in targeting DNA repair deficiencies inherent to these mutations. Bekaii-Saab notes that although FOLFIRINOX remains a widely used platinum-based regimen, other platinum -based regimens, such as the combination of gemcitabine and cisplatin, are also effective in this population.

Bekaii-Saab notes that data from a randomized, phase 2 trial (NCT01585805) led by Eileen O’Reilly, MD, assessing cisplatin and gemcitabine with or without veliparib in patients with germline BRCA- or PALB2-mutated pancreatic cancer have shown favorable outcomes with the doublet. As such, cisplatin-based regimens are now used in certain institutions, with a biweekly cisplatin protocol.

Platinum-based regimens remain the standard for patients who are BRCA1/2 positive in the first-line setting, and further research may continue to refine the role of these mutations in guiding treatment decisions. The ability to tailor therapy based on BRCA mutational status underscores the growing importance of genetic profiling in the management of pancreatic cancer, Bekaii-Saab concludes.