Programmed cell death 1 inhibitor sintilimab plus S-1 and gemcitabine for liver metastatic pancreatic ductal adenocarcinoma.

[BACKGROUND] Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with poor prognosis. When it metastasizes to the liver, treatment options become particularly limited and challenging. Current treatment options for liver metastatic PDAC are limited, and chemotherapy alone often proves insufficient. Immunotherapy, particularly programmed cell death 1 (PD-1) inhibitors like sintilimab, shows potential efficacy for various cancers but has limited reports on PDAC. This study compares the efficacy and safety of sintilimab plus S-1 and gemcitabine S-1 and gemcitabine alone in liver metastatic PDAC.

[AIM] To explore the feasibility and effectiveness of combined PD-1 inhibitor sintilimab and S-1 and gemcitabine (combination group) S-1 and gemcitabine used alone (chemotherapy group) for treating liver metastatic pancreatic adenocarcinoma.

[METHODS] Eligible patients were those with only liver metastatic PDAC, an Eastern Cooperative Oncology Group performance status of 0-1, adequate organ and marrow functions, and no prior anticancer therapy. Participants in the combination group received intravenous sintilimab 200 mg every 3 weeks, oral S-1 40 mg/m² twice daily on days 1-14 of a 21-day cycle, and intravenous gemcitabine 1000 mg/m² on days 1 and 8 of the same cycle for up to eight cycles or until disease progression, death, or unacceptable toxicity. Participants in the chemotherapy group received oral S-1 40 mg/m² twice daily on days 1-14 of a 21-day cycle and intravenous gemcitabine 1000 mg/m² on days 1 and 8 of the same cycle for up to eight cycles. Between June 2020 and December 2021, 66 participants were enrolled, with 32 receiving the combination treatment and 34 receiving chemotherapy alone.

[RESULTS] The group receiving the combined therapy exhibited a markedly prolonged median overall survival (18.8 months compared to 10.3 months, < 0.05) and progression-free survival (9.6 months 5.4 months, < 0.05). compared to the chemotherapy group. The incidence of severe adverse events did not differ significantly between the two groups ( > 0.05).

[CONCLUSION] The combination of PD-1 inhibitor sintilimab with S-1 and gemcitabine demonstrated effectiveness and safety for treating liver metastatic PDAC, meriting further investigation.