A contemporary evidence basis for neoadjuvant chemotherapy in upfront resectable pancreatic adenocarcinoma: A systematic review of the literature

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor survival. Local control through surgical resection paired with radiotherapy and chemotherapy comprise the primary tenets of treatment. Debate exists regarding the timing of treatment and ordering of systemic therapy and resection in the management of early stage disease. The goal of this study was to review the literature and describe the contemporary evidence basis for the role of neoadjuvant therapy (NAT) in the setting of upfront resectable (UP-R) PDAC. Five databases were searched in parallel to identify relevant original articles investigating neoadjuvant therapy where at least 1 study arm contained UP-R PDAC; studies with only borderline resectable or locally advanced disease were excluded. Due to the diversity in NAT regimens and study design between trials, qualitative analyses were performed to investigate patient selection, impact on perioperative and survival outcomes, safety, and cost effectiveness. Thirty-five studies met inclusion criteria, of which 24 unique trials are discussed here in detail. These studies included those trials using single agents as well as more recent trials comparing modern multiagent therapies, and several large database analyses. Overall the data suggest that NAT is safe, may confer survival benefit for appropriately selected patients, is cost effective, and is an appropriate approach for UP-R PDAC. Nevertheless, the risk for disease progression during upfront medical therapy, requires appropriate patient identification and close monitoring, and emphasizes the need for further discovery of more effective chemotherapeutics, useful biomarkers or molecular profiles, and additional prospective comparative studies.