Management of locally advanced/metastatic disease: Medical oncology

Patients with locally advanced or metastatic disease account for the majority of those with newly diagnosed pancreatic cancer. Treatment of both is palliative in nature, and cytotoxic chemotherapy continues to be the only treatment that offers a clear survival benefit. Most oncologists utilize a strategy of induction 5-fluorouracil-(5-FU-) or gemcitabine-based chemotherapy in patients with locally advanced disease, owing to the high likelihood of occult metastatic disease and lack of local therapies that improve survival. However, the role of radiotherapy in locally advanced pancreatic cancer remains an area of interest and investigation. Conversion to surgical resectability is uncommon in the setting of locally advanced disease, but resection should be considered by experienced surgeons for patients responding to chemotherapy, with or without radiation. In the metastatic setting, the development of combination chemotherapy regimens such as gemcitabine + nab-paclitaxel and 5-fluorouracil + folinic acid + irinotecan + oxaliplatin (FOLFIRINOX) has modestly improved patients' life expectancy. The recent approval for the PARP inhibitor, olaparib, as a maintenance therapy for patients with germline BRCA1/2 mutations marks the first biomarker-based approved therapy in pancreatic cancer and has fueled optimism for other targeted therapies. Of note, targeted therapy in unselected patients has not shown clinically significant benefits. To date, immunotherapy has not been effective outside of the small minority with microsatellite instability, but attempts to modulate the pancreatic tumor microenvironment may open the door for future success. Finally, supportive care should not be overlooked as a vital component of managing patients with advanced pancreatic cancer.