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帕博利珠单抗对具有高肿瘤突变负荷的HER2阳性胆囊癌有显著疗效。

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

作者信息

Sasaki Akinori, Nakajima Satoru, Motomura Yasuaki

机构信息

Department of Gastroenterology, Tokyo Bay Urayasu Ichikawa Medical Center, 3-4-32 Toudaijima, Urayasu, Chiba, 279-0001, Japan.

Department of Oncology, Tokyo Bay Urayasu Ichikawa Medical Center, 3-4-32 Toudaijima, Urayasu, Chiba, Japan.

出版信息

J Gastrointest Cancer. 2024 Dec;55(4):1628-1633. doi: 10.1007/s12029-024-01112-9. Epub 2024 Sep 10.

Abstract

PURPOSE

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

摘要

目的

包括胆囊癌在内的晚期胆管癌患者,由于有效的化疗选择有限,预后通常较差。胆管癌患者的基因型导向治疗领域正在不断发展。然而,目前评估分子靶向治疗疗效的临床数据有限。

方法

在此,我们报告一例67岁男性患者,诊断为人类表皮生长因子受体2(HER2)阳性且肿瘤突变负荷高(TMB-H)的胆管癌。在对吉西他滨和S-1治疗耐药后,通过全面基因组分析确定了HER2阳性和TMB-H特征。由于当时尚无针对HER2阳性癌症的临床试验,该患者接受了帕博利珠单抗治疗,帕博利珠单抗在临床实践中用于TMB-H实体瘤。

结果

接受帕博利珠单抗治疗后,患者的原发肿瘤和肝转移灶明显缩小。到目前为止,该患者接受帕博利珠单抗治疗约10个月。

结论

据我们所知,这是首例显示帕博利珠单抗对同时具有HER2阳性和TMB-H的胆管癌患者有效的报告。

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