Immune checkpoint inhibitors have demonstrated broad single-agent antitumor activity and a favorable safety profile that render them attractive agents to combine with other systemic anticancer therapies. Pancreatic cancer has been fairly resistant to monotherapy blockade of programmed cell death protein 1 receptor, programmed death ligand 1, and cytotoxic T-lymphocyte associated protein 4. However, there is a growing body of preclinical evidence to support the rational combination of checkpoint inhibitors and various systemic therapies in pancreatic cancer. Furthermore, early clinical evidence has begun to support the feasibility and efficacy of checkpoint inhibitor-based combination therapy in advanced pancreatic cancer. Despite accumulating preclinical and clinical data, there remains several questions as to the optimal dosing and timing of administration of respective agents, toxicity of combination strategies, and mechanisms by which immune resistance to single-agent checkpoint blockade are overcome. Further development of biomarkers is also important in the advancement of combination systemic therapies incorporating checkpoint blockade in pancreatic cancer. Results from an impressive number of ongoing prospective clinical trials are eagerly anticipated and will seek to validate the viability of combination immuno-oncology strategies in pancreatic cancer.

The multidisciplinary management of locoregional esophagogastric cancers (GCs) has evolved significantly over the past two decades. While perioperative chemotherapy, adjuvant chemotherapy, and postoperative chemotherapy with chemoradiation (CRT) have demonstrated improved survival when compared to surgery alone, there is no universal standard for resectable gastroesophageal cancer. Current global management patterns vary by geographic region, partly related to phase III data originating from each global region. Herein we detail the landmark phase III trials that support the various multimodality treatment paradigms in resectable GC, with particular focus on findings from more recent phase III gastroesophageal cancer trials including FLOT4, MAGIC-B, OE05, and CRITICS. We highlight important ongoing and future approaches including the potential of molecular subtyping, predictive biomarkers, and immunotherapy as avenues to further improve outcomes in resectable gastroesophageal cancer.

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Future studies in treatment-refractory mCRC may be better served by evaluating improvement in symptom control and QOL, which may otherwise serve as the best predictor of survival in last-line treatment settings.