Challenges and Opportunities for the Clinical Application of the Combination of Immune-Checkpoint Inhibitors and Radiation Therapy in the Treatment of Advanced Pancreatic Cancer.

The treatment landscape of pancreatic ductal adenocarcinoma (PDAC) has seen slow progress, with immune-checkpoint inhibitors (ICIs) failing to replicate the success observed in other malignancies. The immune-suppressive tumor microenvironment (TME) in PDAC represents a significant barrier, limiting the activation of an effective antitumor immune response following ICI administration. Radiation therapy (RT), with its immunomodulatory effects, has emerged as a promising partner for ICIs. This review discusses the recent efforts evaluating the combination of ICIs and RT in advanced PDAC. While the combination therapy has demonstrated an acceptable safety profile, the reported clinical efficacy remains modest, particularly for patients with refractory metastatic PDAC. The ongoing phase III trial (JCOG1908E) will clarify whether the combination of ICI and RT improves overall survival in chemo-naïve patients with locally advanced PDAC.