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, Abby B Siegel, 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
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.
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References
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Source: PubMed