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Poster display session

3144 - HER-2/HER-3 pathway as a potentially-actionable target in biliary tract cancers (BTCs): a retrospective analysis

Date

09 Sep 2017

Session

Poster display session

Presenters

Angela Lamarca

Citation

Annals of Oncology (2017) 28 (suppl_5): v209-v268. 10.1093/annonc/mdx369

Authors

A. Lamarca1, S. Galdy1, S. Moghadam2, J. Rogan2, M.G. McNamara3, R.A. Hubner1, A. Cramer4, J.W. Valle5

Author affiliations

  • 1 Medical Oncology, The Christie NHS Foundation Trust, M20 4BX - Manchester/GB
  • 2 Biobank, Manchester Cancer Reseacrh Centre, University of Manchester, M20 4BX - Manchester/GB
  • 3 Medical Oncology, The University of Manchester / The Christie, M204BX - Manchester/GB
  • 4 Pathology Partnership, The Christie NHS Foundation Trust, M20 4BX - Manchester/GB
  • 5 Medical Oncology, The University of Manchester / The Christie, Manchester/GB
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Resources

Abstract 3144

Background

Cholangiocarcinoma (CC), gallbladder cancer (GBC) and ampullary cancer (AC) (collectively BTCs) are poor-prognosis cancers. Cisplatin-gemcitabine chemotherapy is the standard treatment for patients (pts) with advanced BTC. New treatment targets are warranted; the human epidermal growth factor receptor (HER)-2 and HER-3 pathways may be potential candidates. High-quality data regarding expression and/or amplification rates in BTC are lacking.

Methods

Pts diagnosed with BTC and with available paraffin-embedded archival tissue were eligible. Seventy consecutive pts were required (power 0.91; assumptions: 5% (no expression) vs. 15% (expression of interest); α-error 0.1). All pts had been previously consented for tissue storage for research purposes. The study was approved by the local BioBank Ethics Committee. Overexpression of HER-2 and HER-3 was analysed by immunohistochemistry (IHC) following standard guidelines (gastric criteria were followed for HER-2); samples with “2+; borderline” IHC expression underwent additional fluorescence in-situ hybridisation (FISH). Kaplan Meier and Cox Regression analyses were employed for survival. Logistic regression was used to identify factors associated with HER overexpression.

Results

Of 167 screened pts between Jan-13 and Jul-15, 76 samples were retrieved for quality assessment; 67 were eligible with a median age of 65.6 years (range 32.9-79.3); 51.2% were female; 85.1% had ECOG performance status 0-1; all were adenocarcinomas. Primary site was GBC (n = 10, 14.9%), CC (n = 44, 65.7%; n = 26 intra-hepatic (ICC), n = 18 extra-hepatic (ECC)) and AC (n = 13, 19.4%). Stage at diagnosis: I/II (n = 21, 31.3%) or III/IV (n = 46, 68.7%). Estimated median overall survival (OS) for all pts was 15.9 months (95% CI 11.1-20.3). HER-2 overexpression was identified in 1 pt (1.5%). HER-3 overexpression was identified in 16 (23.9%): 1 pt was classified as “3+; positive” by IHC and 15 were confirmed by FISH following a “2+” expression in IHC. Neither HER-2 (p = 0.103) nor HER-3 (p = 0.087) impacted on OS. No factors related to HER-3 overexpression were identified.

Conclusions

HER-3 is overexpressed in a significant subset of pts diagnosed with BTC; treatment targeting this pathway may warrant evaluation.

Clinical trial identification

n/a

Legal entity responsible for the study

MCRC Biobank

Funding

Dr Lamarca was part-funded by Pancreatic Cancer Research Fund (PCRF) Grant and Spanish Society of Medical Oncology (SEOM) Fellowship Grant. Dr Galdy was part-funded by “Clinical Unit Visit” European Society of Medical Oncology (ESMO) Fellowship.

Disclosure

All authors have declared no conflicts of interest.

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