PD-1 blockade plus capecitabine as curative-intent treatment for tumor mutational burden-high multi-metastatic pancreatic ductal adenocarcinoma: A case report

The rising incidence and persistently dismal 5-year overall survival of pancreatic ductal adenocarcinoma (PDAC) highlight the need for effective new systemic therapies. Cancer immunotherapy has increasingly garnered attention. Various methods, such as cell therapy, immune-checkpoint blockers (ICBs), and cancer vaccines, alone or in combination, have achieved satisfactory results in cancer therapy. Immunotherapy has shown significant benefits in solid organ tumors but has been disappointing in PDAC treatment. Despite promising preclinical studies, clinical translation has proven challenging, possibly because PDAC has a complex immunosuppressive tumor microenvironment (TME), which insulates the tumor from an effective cytotoxic immune response. Therefore, we aimed to investigate combined approaches to improve ICB efficacy. Here we present a case of a 69-year-old man diagnosed with multi-metastatic PDAC. Genetic analysis revealed a high tumor mutational burden of 9.02 mutations/megabase. The TME was positive for CD4 ⁺ and CD8 ⁺ T cells, suggesting potential immunotherapy success. Immune-checkpoint blockade treatment with sintilimab, a programmed cell death protein 1 (PD-1) monoclonal antibody, was initiated, leading to disease regression. The treatment response was confirmed using contrast-enhanced magnetic resonance imaging and computed tomography.