Prolonged Response to HER2-Directed Therapy in Three Patients with HER2-Amplified Metastatic Carcinoma of the Biliary System: Case Study and Review of the Literature

Abstract

HER2 amplification, which results in overexpression of the receptor tyrosine kinase HER2, has been described in a wide variety of malignancies. HER2-targeting agents have been incorporated into the treatment paradigms for HER2overexpressing breast and gastric cancer. More recently, these agents have shown promise in other gastrointestinal malignancies, such as colon cancer and biliary tract tumors. Herein we discuss two patients with gallbladder carcinoma (GBC) and a third with ampullary carcinoma who were able to achieve marked responses to HER2-directed therapy. These cases underscore the importance of molecular analysis for HER2 amplification/HER2 overexpression, irrespective of tumor histology, and highlight a need for further investigation of HER2-directed therapy beyond breast and gastroesophageal cancers. The Oncologist 2021;9999:• • KEY POINTS• Current guidelines recommend molecular assessment for HER2-oversexpression exclusively in breast and gastric adenocarcinoma • The focus of this report is on three cases (two biliary tract and one ampullary carcinoma) in which amplification of HER2 or overexpression of HER2 is detected and treatment with HER2-directed therapy resulted in robust responses • These cases exemplify responsiveness of non-breast/gastric histologies to HER2-directed therapies, highlighting several promising new settings for these agents • Testing for amplification of HER2 or overexpression of HER2 should be considered especially in rare diseases with limited treatment options

Molecular pathology for cholangiocarcinoma: a review of actionable genetic targets and their relevance to adjuvant & neoadjuvant therapy, staging, follow-up, and determination of minimal residual disease

“…HER2 overexpression and gene amplifications are found most commonly in extrahepatic CCA and GBC, at a rate of 17–19% ( 32 ). Although case reports suggest that patients with HER2 overexpression respond to HER2-targeting antibodies ( 33 , 34 ), initial phase I and II clinical trials employed broad inhibitors of EGFR and HER2 (lapatinib or afatinib) and failed to demonstrate any significant benefit ( 35 - 37 ). These trials were performed in an unselected group of patients, two of which later found no evidence of HER2 overexpression in any participant.…”

Current and Emerging Therapeutic Targets for the Treatment of Cholangiocarcinoma: An Updated Review

“…A retrospective study of HER-2-directed therapy, including trastuzumab, pertuzumab, or lapatinib, suggested sustained response to these agents among nine patients with HER-2 mutated gallbladder cancer. However, despite a higher incidence of HER-2 mutations in cholangiocarcinoma compared with gallbladder cancers, five patients with HER-2 mutated cholangiocarcinoma showed no response to HER-2-directed therapy in the same study [ 36 ].…”

Machine learning models for predicting survival in patients with ampullary adenocarcinoma

“… 1 , 2 The incidence of AAC is estimated to be 0.5, 0.73, and 0.96 per 100,000 persons per year in the US, Japan, and the Netherlands, respectively. 3 , 4 , 5 Despite its rarity, the occurrence of AAC has increased worldwide over the past few decades. 6 , 7 Patients with AAC tend to present typical symptoms of biliary obstruction at relatively early stages, but these symptoms are mostly non-specific and are therefore often detected incidentally during examinations.…”

“…that originates in biliary, duodenal, or pancreatic ductal epithelial cells 1,2 . The incidence of AAC is estimated to be 0.5, 0.73, and 0.96 per 100,000 persons per year in the US, Japan, and the Netherlands, respectively [3][4][5] . Despite its rarity, the occurrence of AAC has increased worldwide over the past few decades 6,7 .…”