Maintenance Treatment for Metastatic Pancreatic Cancer: Balancing Therapeutic Intensity with Tolerable Toxicity

Simple Summary Metastatic pancreatic cancer is conventionally treated with chemotherapy until the development of either progressive disease or intolerable cumulative toxicity. Maintenance treatment refers to the concept of de-escalating therapy, either by paring back on the components of multi-agent chemotherapy or by the introduction of novel agents, in patients who have achieved a favorable response (stable disease or better) following a period of first-line chemotherapy. The goal of maintenance treatment is to maintain disease control and maximize progression-free intervals while preserving or improving patients' quality of life and minimizing cumulative toxicity. Here, we summarize the existing data to guide the use of maintenance treatments and discuss future directions in the field. Metastatic pancreatic ductal adenocarcinoma is typically treated with multi-agent chemotherapy until disease progression or intolerable cumulative toxicity. For patients whose disease shows ongoing control or response beyond a certain timeframe (& GE;3-4 months), options include pausing chemotherapy with close monitoring or de-escalating to maintenance therapy with the goal of prolonging progression-free and overall survival while preserving quality of life. There is currently no universally accepted standard of care and a relative dearth of randomized clinical trials in the maintenance setting. Conceptually, such therapy can entail continuing the least toxic components of a first-line regimen and/or introducing novel agent(s) such as the poly(ADP-ribose) polymerase inhibitor olaparib, which is presently the only approved drug for maintenance treatment and is limited to a genetically defined subset of patients. In addition to identifying new therapeutic candidates and combinations in the maintenance setting, including targeted agents and immunotherapies, future research should focus on better understanding this unique biologic niche and how treatment in the maintenance setting may be distinct from resistant/refractory disease; identifying molecular predictors for more effective pairing of specific treatments with patients most likely to benefit; and establishing patient-reported outcomes in clinical trials to ensure accurate capture of quality of life metrics.