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HER2/neu-directed therapy for biliary tract cancer

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...

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Autores principales: Javle, Milind, Churi, Chaitanya, Kang, HyunSeon C., Shroff, Rachna, Janku, Filip, Surapaneni, Rakesh, Zuo, Mingxin, Barrera, Christian, Alshamsi, Humaid, Krishnan, Sunil, Mishra, Lopa, Wolff, Robert A., Kaseb, Ahmed O., Thomas, Melanie B., Siegel, Abby B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4469402/
https://www.ncbi.nlm.nih.gov/pubmed/26022204
http://dx.doi.org/10.1186/s13045-015-0155-z
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author Javle, Milind
Churi, Chaitanya
Kang, HyunSeon C.
Shroff, Rachna
Janku, Filip
Surapaneni, Rakesh
Zuo, Mingxin
Barrera, Christian
Alshamsi, Humaid
Krishnan, Sunil
Mishra, Lopa
Wolff, Robert A.
Kaseb, Ahmed O.
Thomas, Melanie B.
Siegel, Abby B.
author_facet Javle, Milind
Churi, Chaitanya
Kang, HyunSeon C.
Shroff, Rachna
Janku, Filip
Surapaneni, Rakesh
Zuo, Mingxin
Barrera, Christian
Alshamsi, Humaid
Krishnan, Sunil
Mishra, Lopa
Wolff, Robert A.
Kaseb, Ahmed O.
Thomas, Melanie B.
Siegel, Abby B.
author_sort Javle, Milind
collection PubMed
description 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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spelling pubmed-44694022015-06-18 HER2/neu-directed therapy for biliary tract cancer Javle, Milind Churi, Chaitanya Kang, HyunSeon C. Shroff, Rachna Janku, Filip Surapaneni, Rakesh Zuo, Mingxin Barrera, Christian Alshamsi, Humaid Krishnan, Sunil Mishra, Lopa Wolff, Robert A. Kaseb, Ahmed O. Thomas, Melanie B. Siegel, Abby B. J Hematol Oncol Research Article 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. BioMed Central 2015-05-29 /pmc/articles/PMC4469402/ /pubmed/26022204 http://dx.doi.org/10.1186/s13045-015-0155-z Text en © Javle et al. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Javle, Milind
Churi, Chaitanya
Kang, HyunSeon C.
Shroff, Rachna
Janku, Filip
Surapaneni, Rakesh
Zuo, Mingxin
Barrera, Christian
Alshamsi, Humaid
Krishnan, Sunil
Mishra, Lopa
Wolff, Robert A.
Kaseb, Ahmed O.
Thomas, Melanie B.
Siegel, Abby B.
HER2/neu-directed therapy for biliary tract cancer
title HER2/neu-directed therapy for biliary tract cancer
title_full HER2/neu-directed therapy for biliary tract cancer
title_fullStr HER2/neu-directed therapy for biliary tract cancer
title_full_unstemmed HER2/neu-directed therapy for biliary tract cancer
title_short HER2/neu-directed therapy for biliary tract cancer
title_sort her2/neu-directed therapy for biliary tract cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4469402/
https://www.ncbi.nlm.nih.gov/pubmed/26022204
http://dx.doi.org/10.1186/s13045-015-0155-z
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