Abstract
HER2 amplification/overexpression is a common driver in a variety of cancers including gallbladder cancer (GBC). For patients with metastatic GBC, chemotherapy remains the standard of care with limited efficacy. The combination of HER2 antibody trastuzumab plus chemotherapy is the frontline treatment option for patients with HER2-positive breast cancer and gastric cancer. Recently, this regime also showed antitumor activity in HER2-positive GBC. However, resistance to this regime represents a clinical challenge. Camrelizumab is a novel PD-1 antibody approved for Hodgkin lymphoma and hepatocellular carcinoma in China. In this study, we presented a HER2-positive metastatic GBC patient who was refractory to trastuzumab plus chemotherapy but experienced significant clinical benefit after the addition of camrelizumab. Our case highlights the potential of immunotherapy in combination with HER2-targeted therapy in HER2-positive GBC. We also demonstrated that two immune-related adverse events (irAEs) associated with camrelizumab can be managed with an anti-VEGF agent apatinib. This case not only highlights the importance of irAE management in patients treated with camrelizumab, but also demonstrates the potential of PD-1 antibody plus trastuzumab in HER2-positive GBC patients who have developed resistance to chemotherapy and trastuzumab-based targeted therapy.
Highlights
Biliary tract cancers (BTCs) are low-incidence epithelial malignancies in the biliary tree, including gallbladder cancer (GBC) and cholangiocarcinoma (CCA)
BTCs are generally refractory to chemotherapy and the 5-year survival rate of BTC patients ranges from 5% to 15% [22]
HER2 overexpression is detected in 13%-31% of GBC cases and is a promising candidate for targeted therapy clinical trials [23,24,25]
Summary
Biliary tract cancers (BTCs) are low-incidence epithelial malignancies in the biliary tree, including gallbladder cancer (GBC) and cholangiocarcinoma (CCA). A variety of HER2-directed agents including monoclonal antibodies, tyrosine kinase inhibitors, and antibody-drug conjugates (ADCs), have significantly improved the outcomes of patients with HER2-positive breast cancer and become the front-line treatment options for this disease [8]. In a singlecenter phase 2 trial, the combination of pembrolizumab plus trastuzumab and chemotherapy achieved a disease control rate of 100% and an objective response rate (ORR) of 83% in HER2positive metastatic esophagogastric adenocarcinoma irrespective of PD-L1 status [14]. Based on these results and the affordability of a. The patient remained in remission until the last follow-up in November 2021 with a KPS score of 90
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