Durable response to capecitabine plus pembrolizumab in synchronous intrahepatic cholangiocarcinoma and gastric adenocarcinoma: a case report

Background Multiple primary malignancies (MPMs) are uncommon, and synchronous occurrence of gastric cancer with intrahepatic cholangiocarcinoma (ICC) is extremely rare, with only isolated case reports documented. Most reported cases were managed surgically, and data on systemic therapy remain limited, with no established treatment guidelines for this specific population. Case presentation An asymptomatic 87-year-old female was diagnosed with synchronous poorly differentiated ICC and primary gastric adenocarcinoma. Next-generation sequencing of the hepatic lesion revealed an FGFR3-TACC3 fusion and a high Ki-67 index of 70%, with low tumor mutational burden and microsatellite stable status. The gastric tumor was proficient mismatch repair (pMMR) and HER2-negative. Due to her advanced age and refusal of standard intravenous chemotherapy, she received a low-toxicity regimen of oral capecitabine (1,000 mg/m² orally twice daily on days 1–14) and intravenous pembrolizumab (200 mg on day 1) in 21-day cycles. Remarkably, the patient achieved a sustained radiographic partial response, with a progression-free survival (PFS) of 38.7 months as of the last radiological assessment on June 18, 2026. The treatment was generally well tolerated, with grade 1 hand-foot syndrome and grade 1 leukopenia and no grade 3 or higher adverse events. Conclusion This is the first reported case of synchronous intrahepatic cholangiocarcinoma and gastric adenocarcinoma showing durable response to pembrolizumab plus capecitabine.