703P - HER2/HER3 pathway in biliary tract cancers: A systematic review and meta-analysis. A novel therapeutic druggable target?

Date 08 October 2016
Event ESMO 2016 Congress
Session Poster Display
Topics Hepatobiliary Cancers
Presenter Salvatore Galdy
Citation Annals of Oncology (2016) 27 (6): 207-242. 10.1093/annonc/mdw371
Authors S. Galdy1, A. Lamarca2, M. McNamara2, R. Hubner2, C.A. Cella1, N. Fazio1, J.W. Valle2
  • 1Gastrointestinal And Net Unit, Istituto Europeo di Oncologia, 20141 - Milano/IT
  • 2Medical Oncology, The Christie NHS Foundation Trust, M20 4BX - Manchester/GB

Abstract

Background

HER2 overexpression and/or amplification has been reported as predictive factor to HER2 targeted therapy in breast and gastric cancer, whereas HER3 is emerging as a potential resistance factor. The aim of this study was to perform a systematic review and meta-analysis of the HER2 and HER3 up-regulation in biliary tract cancers (BTCs).

Methods

An electronic search of MEDLINE, ASCO, ESMO and AACR was performed to identify studies reporting HER2 and/or HER3 membrane protein expression by immunohistochemistry (IHC) and/or gene amplification by in situ hybridisation (ISH) in BTCs.

Results

Out of 440 studies screened, 40 met the inclusion criteria. Globally, HER2 expression rate was 26.5% (95% CI, 18.9% - 34.1%). Studies were classified as “high-quality” (HQ; 27 studies) [IHC overexpression defined as presence of moderate/strong staining] and “low-quality” (11 studies) [“any” expression was considered positive]. When HQ studies were analysed, extra-hepatic BTCs (EH-BTCs) showed a higher HER2 overexpression rate compared to intrahepatic cholangiocarcinoma (IHCC) [19.9% (95% CI, 12.8 – 27.1%) vs. 4.8% (95% CI, 0 – 14.5%); p-value 0.0049]. HER2 amplification rate was higher in those patients selected by HER2 overexpression [57.6% (95% CI, 16.2 - 99%)] compared to “unselected” patients [17.9% (95% CI, 0.1 – 35.4%); p-value 0.0072]. HER3 overexpression (4/4 HQ studies) and amplification rates were 27.9% (95% CI, 9.7 - 46.1%) and 26.5% (one study), respectively.

Conclusions

Up to 20% of EH-BTCs might be HER2 overexpressed, ∼60% of HER2 overexpressed BTCs can be considered amplified while HER3 is overexpressed or amplified in ∼25% of BTCs. These findings may be considered in future trial development.

HER2 status No. studies Up-regulation rate mean (95% CI, %) P-Value
Overall expression by IHC 38 26.5% (18.9 - 34.1%)
Region of provenience Asia 17 28.4% (14.5 - 42.3%)
West 16 19.7% (10.1 - 29.2%) 0.4936
IHC assessment Low quality 11 41.7% (22.9 - 60.5%)
High quality 27 20.3% (13.2 - 27.5%) 0.0336
Site of Primary regardless IHC scoring IHCC 12 21.1% (2.3 - 39.7%)
EHBTC 32 22.5% (15.5 - 29.5%) 0.2557
EHCC 11 17.4% ( 3.4 - 31.4%) 0.4752
GBC 14 24.2% (14.1 - 34.3%) 0.2339
AC 7 27.2% (7.2 - 47.2%) 0.4652
Site of Primary by HQ/IHC IHCC 8 4.8% (0 - 14.5%)
EHBTC 28 19.9% (12.8 - 27.1%) 0.0049
EHCC 11 17.4% ( 3.4 - 31.4%) 0.0134
GBC 12 19.1% ( 11.2 - 26.8%) 0.0123
AC 5 27.9% (0 - 60.7%) 0.0642
Overall amplification by ISH 16 30.1% (11.7 - 48.5%)
Site of Primary IHCC 6 17.6% (0 - 60.1%)
EHBTC 14 22.5% (7.9 - 37.2%) 0.0468
Amplification by selection population No 12 17.9% (0.1 - 35.4%)
Yes 5 57.6% (16.2 - 99%) 0.0072

Clinical trial identification

Legal entity responsible for the study

Istituto Europeo di Oncologia, Milano (IT)

Funding

“Clinical Unit Visit” ESMO fellowship

Disclosure

All authors have declared no conflicts of interest.