HER2/neu-directed therapy for biliary tract cancer

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 and Abby B. Siegel
Javle et al. Journal of Hematology & Onclogy (2015) 8:58; doi 10.11186/s13045-015-0155-z

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.

Keywords: Receptor, ErbB-2, Gallbladder neoplasms, Cancer of the biliary tract

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