Exceptional Response to Pembrolizumab in HER2-Positive Gallbladder Carcinoma with High Tumor Mutational Burden

Patients with advanced cholangiocarcinoma, including gallbladder cancer, typically have a poor prognosis owing to limited effective chemotherapy options. The field of genotype-directed therapy in patients with cholangiocarcinoma is advancing. However, limited clinical data are currently available to evaluate the efficacy of molecularly targeted therapy.

Herein, we report the case of a 67-year-old man diagnosed with human epidermal growth factor receptor-2 (HER2)–positive and tumor mutation burden-high (TMB-H) cholangiocarcinoma. The HER2-positive and TMB-H characteristics were identified using comprehensive genomic profiling after showing resistance to gemcitabine and S-1 therapy. In the absence of clinical trials for HER2-positive cancer at that time, the patient was treated with pembrolizumab, which is used for TMB-H solid tumors in clinical practice.

After receiving pembrolizumab, the patient experienced significant shrinkage in the primary tumor and liver metastases. Thus far, the patient has been receiving pembrolizumab for approximately 10 months.

To our knowledge, this is the first report showing the efficacy of pembrolizumab in a patient with cholangiocarcinoma harboring both HER2-positive and TMB-H.