HER2/neu-directed therapy for biliary tract cancer.

Abstract

BACKGROUND:

Biliary cancers are highly aggressive tumors that are often diagnosed an advanced disease stage and have a poor outcome with systemic therapy. Recent efforts towards molecular characterization have identified a subset of biliary patients that have HER2/neu amplification or mutation. HER2/neu amplification is associated with response to HER2/neu-directed therapy in breast and gastric cancers. However, the efficacy of HER2/neu-targeted therapy in biliary cancers is unknown.

PATIENTS AND METHODS:

We retrospectively reviewed cases of advanced gallbladder cancer and cholangiocarcinoma with HER2/neu genetic aberrations or protein overexpression who received HER2/neu-directed therapy between 2007 and 2014. Clinical data were retrieved from medical records, and imaging studies were independently reviewed.

RESULTS:

Nine patients with gallbladder cancer and five patients with cholangiocarcinoma had received HER2/neu-directed therapy (trastuzumab, lapatinib, or pertuzumab) during the study period. In the gallbladder cancer group, HER2/neu gene amplification or overexpression was detected in eight cases. These patients experienced disease stability (n = 3), partial response (n = 4), or complete response (n = 1) with HER2/neu-directed therapy. One patient had HER2/neu mutation and experienced a mixed response after lapatinib therapy. The duration of response varied from 8+ to 168 weeks (median 40 weeks), and three patients are still on therapy. One patient developed HER2/neu amplification as a secondary event after FGFR-directed therapy for FGF3-TACC3 gene fusion. The cholangiocarcinoma cases treated in this series had a higher proportion of HER2/neu mutations, and no radiological responses were seen in these patients despite HER2/neu-directed therapy.

CONCLUSIONS:

HER2/neu blockade is a promising treatment strategy for gallbladder cancer patients with gene amplification and deserves further exploration in a multi-center study.

• Authors: Milind Javle, Chaitanya Churi, HyunSeon C Kang, Rachna Shroff, Filip Janku, Rakesh Surapaneni, Mingxin Zuo, Christian Barrera, Humaid Alshamsi, Sunil Krishnan, Lopa Mishra, Robert A Wolff, Ahmed O Kaseb, Melanie B Thomas, Abby B Siegel
• Journal: Journal of hematology & oncology (J Hematol Oncol) Vol. 8 Pg. 58 (May 29 2015) ISSN: 1756-8722 [Electronic] England
• PMID: 26022204 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ERBB2 protein, human
• Receptor, ErbB-2

Topics

• Adult
• Biliary Tract Neoplasms (genetics, therapy)
• Female
• Gallbladder Neoplasms (genetics)
• Humans
• Immunohistochemistry
• Male
• Middle Aged
• Receptor, ErbB-2 (genetics)
• Retrospective Studies
• Young Adult