Pathological complete response following addition of durvalumab to gemcitabine and cisplatin therapy for intrahepatic cholangiocarcinoma with Lynch syndrome-associated mismatch repair deficiency.

A 64-year-old man with a history of surgery for rectal cancer and colon cancer was referred for a hepatic mass identified on computed tomography (CT). He was diagnosed with unresectable intrahepatic cholangiocarcinoma (ICC) with perihilar and para-aortic lymph node metastases. After 4 cycles of gemcitabine and cisplatin combination therapy (GC therapy), follow-up CT showed slight enlargement of the primary tumor and a slight increase in carbohydrate antigen (CA) 19-9. Genetic testing was performed during GC therapy based on the strong family history of cancer. Germline pathogenic variant in MLH1 was identified, leading to the diagnosis of Lynch syndrome (LS) with mismatch repair deficiency (dMMR: loss of MLH1/PMS2). Durvalumab was added to GC therapy following regulatory approval in Japan. A significant reduction in tumor size and CA19-9 was observed after only two cycles of GC and durvalumab therapy. Continuous improvement was observed, and conversion surgery involving liver resection, partial inferior vena cava resection, and perihilar and para-aortic lymph nodes dissection was performed with curative intent. No malignant cells were found in any of the resected specimens, consistent with pathological complete response.