Association between HER2 amplification and cetuximab efficacy in patients with RAS wild-type metastatic colorectal cancer

Date

08 Oct 2016

Session

Poster Display

Presenters

Jaeho Jeong

Citation

Annals of Oncology (2016) 27 (6): 149-206. 10.1093/annonc/mdw370

Authors

J. Jeong1, J. Kim2, Y.S. Hong3, D. Kim1, J.E. Kim3, S.Y. Kim3, K. Kim3, T.W. Kim1

Author affiliations

  • 1 Department Of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 05505 - Seoul/KR
  • 2 Department Of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul/KR
  • 3 Department Of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul/KR
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Background

Cetuximab has shown clinical benefit in patients with metastatic colorectal cancer (mCRC) harbouring wild-type RAS. HER2 amplification has been suggested as one of the resistant mechanisms of cetuximab treatment. We evaluated association between HER2 amplification and cetuximab efficacy in mCRC patients harbouring extended RAS wild-type.

Methods

Between December 2003 and June 2013, we found 253 mCRC patients whose tumor harboured wild type in exon 2/3/4 both of KRAS and NRAS by high throughput sequencing (OncoMap version 4.0) and were treated with cetuximab as 2nd or later-line. We finally included 243 mCRC cases whose HER2 status could be determined by both immunohistochemical (IHC) scoring according to HERACLES criteria and silver in-situ hybridisation (SISH). Progression-free survival (PFS) and overall survival (OS) were analysed in homogenous group (n = 149) who were progressed after oxaliplatin, irinotecan and fluoropyrimidines.

Results

The median age was 55 years (range 19–76 years); 168 patients (69.1%) were male. Of the 243 RAS wild-type tumor, we observed 11 cases (4.5%) of HER2 amplification (table). After the median follow-up of 13.5 months (range, 0.4–78.1), median PFS was statistically different according to the HER2 status: 3.1 months in patients harbouring HER2 amplification vs 5.7 months in those harbouring non-amplified HER2 (p = 0.013). OS was not statistically different according to the HER2 status although there was a tendency towards shorter OS in patients harbouring HER2 amplification (10.1 vs 13.5 months, p = 0.408).

HER2 IHC (HERACLES criteria)
SISH Negative Equivocal Positive Total
Amplification 1 1†† 9††† 11
No amplification 229 3 0 232
Total 230 4 9 243

HER2/CEP17 ratio 3.3, †† HER2/CEP17 ratio 2.7, ††† HER2/CEP17 ratio >5 (all cases)

Conclusions

HER2 amplification is associated with shorter PFS after cetuximab in mCRC patients harbouring extended RAS wild-type. Recent study of dual targeting of EGFR and HER2 demonstrated promising result; further study is warranted for this population.

Clinical trial identification

Legal entity responsible for the study

Asan Medical Center

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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