With the advent of multiagent chemotherapy for metastatic pancreatic cancer, subgroups of patients whose disease responds durably to treatment are emerging. Although this is wonderful progress in the face of a deadly illness, cumulative toxicities of perpetual chemotherapy over months or even years of treatment degrade quality of life and organ function, in addition to fueling eventual therapeutic resistance. The POLO trial demonstrated a benefit of maintenance olaparib compared with placebo in patients with germline pathogenic variants in BRCA1 or BRCA2. The success of this trial, albeit in a limited subset of patients, suggests that there may be opportunity to study this alternative treatment strategy as a paradigm for a broader group of patients with advanced pancreatic cancer. This article discusses the phenotypic and genotypic signatures of patients with pancreatic cancer that may provide the basis upon which to design rational maintenance clinical trials.