Nandini Ray, MD, Dayoung Jeon, MD, Ahmad Afzal, MD, Apaar Dadlani, MD, Nakul Gupta, MD, Ashish Saharia, MD, Sudha Kodali, MD Houston Methodist Hospital, Houston, TX Introduction: Human epidermal growth factor receptor 2 (HER2) is an important biomarker that plays a critical role in breast and gastric cancer. Recent literature demonstrates that HER2 is involved in biliary tract cancers, which are traditionally known as being harder to treat with a poorer prognosis due to high heterogeneity. However, this unique feature allows for an opportunity for personalized, targeted therapies.
Case Description/
Methods: A 59-year-old male with past medical history significant for hypertension, hypothyroidism, and coronary artery disease presented with right upper quadrant abdominal pain and recurrent fevers. Initial workup with computed tomography of the abdomen and pelvis with contrast was significant for multiple bilobar hepatic lesions with peripheral enhancement and central necrosis, suspicious for cholangiocarcinoma. Subsequent positron emission tomography scan was significant for extensive hypermetabolic masses in both liver lobes without evidence of other active lesions. Liver biopsy was significant for poorly differentiated intrahepatic cholangiocarcinoma, with tumor cells diffusely positive for CK7 and CK19. He was initiated on first-line chemotherapy with gemcitabine, cisplatin, and durvalumab. On subsequent surveillance imaging performed four months following initiation of chemotherapy, patient was noted to have progression in size of his liver lesions. Due to progression of disease, next-generation sequencing was performed following repeat liver biopsy and was significant for HER2 (ERBB2) positivity and amplification. His chemotherapy regimen was switched to second-line therapy with trastuzumab with improvement of disease burden on subsequent imaging. He underwent successful orthotopic liver transplant, with biopsy findings of the explanted liver significant for four tumor nodules with complete tumor necrosis and no viable tumor. Biopsy findings were classified as pT0pN0, indicating no evidence of residual tumor, vascular invasion, or spread to regional lymph nodes.
Discussion: This is a case of a patient presenting with HER2-positive intrahepatic cholangiocarcinoma who demonstrated excellent response to HER2-targeted therapy. Although liver resection is the only curative option for intrahepatic cholangiocarcinoma, prognosis often remains poor following surgery. Few reported cases exist describing this promising association, so further characterization of regimens with anti-HER2 therapies may pave the way for more durable responses.
Figure: Figure 1. A. Representative section from computed tomography of the abdomen/pelvis with contrast at time of initial diagnosis before treatment with HER2-targeted therapy demonstrating bilobar hypo-vascular masses (red arrows). B. Follow-up computed tomography of the abdomen and pelvis with contrast obtained four months following initiation of HER2-targeted therapy, demonstrating diminished enhancement of the masses related to treatment effect as well as more pronounced capsular retraction and pseudo-cirrhotic changes in the liver. New onset perihepatic ascites noted (red arrow).
Figure: Figure 2. Follow-up computed tomography of the abdomen/pelvis with contrast obtained three months following orthotopic liver transplant. Surgical clips noted at caval anastomosis (red arrow).
Disclosures: Nandini Ray indicated no relevant financial relationships. Dayoung Jeon indicated no relevant financial relationships. Ahmad Afzal indicated no relevant financial relationships. Apaar Dadlani indicated no relevant financial relationships. Nakul Gupta indicated no relevant financial relationships. Ashish Saharia indicated no relevant financial relationships. Sudha Kodali: ASTRAZENECA – Advisory Committee/Board Member. GILEAD – Advisor or Review Panel Member, Advisory Committee/Board Member, Speakers Bureau. SIRTEX – Advisor or Review Panel Member.
Nandini Ray, MD, Dayoung Jeon, MD, Ahmad Afzal, MD, Apaar Dadlani, MD, Nakul Gupta, MD, Ashish Saharia, MD, Sudha Kodali, MD. P4459 - Intrahepatic Cholangiocarcinoma With Excellent Response to HER2-Targeted Therapy, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.
