HER2 Amplification and Cetuximab Efficacy in Patients With Metastatic Colorectal Cancer Harboring Wild-type RAS and BRAF

Jae Ho Jeong, Jihun Kim, Yong Sang Hong, Dalyong Kim, Jeong Eun Kim, Sun Young Kim, Kyu pyo Kim, Young Kwang Yoon, Deokhoon Kim, Sung Min Chun, Yangsoon Park, Se Jin Jang, Tae Won Kim

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33 Scopus citations

Abstract

Human epidermal growth factor receptor 2 (HER2) amplification may be a mechanism of cetuximab resistance. We evaluated the association between HER2 amplification and cetuximab efficacy in 142 patients with metastatic colorectal cancer harboring wild-type RAS and BRAF. We found that HER2 amplification is predictive of shorter progression-free survival after cetuximab treatment in patients with metastatic colorectal cancer harboring wild-type RAS and BRAF. Background Cetuximab has shown clinical benefit in patients with metastatic colorectal cancer (mCRC) harboring wild-type RAS. Human epidermal growth factor receptor 2 (HER2) amplification may be a mechanism of cetuximab resistance. We evaluated the association between HER2 amplification and cetuximab efficacy in patients with mCRC harboring wild-type RAS and BRAF. Patients and Methods Between December 2003 and June 2013, we identified 142 patients with mCRC whose tumors harbored both wild-type exons 2, 3, and 4 in KRAS and NRAS, and wild-type exon 15 in BRAF using high throughput sequencing (OncoMap version 4.0). All patients received cetuximab after oxaliplatin, irinotecan, and fluoropyrimidine failure. HER2 status was determined using immunohistochemistry and silver in situ hybridization (SISH) and correlated with cetuximab efficacy. Results Of 142 RAS and BRAF wild-type tumors, we observed 7 cases (4.9%) of HER2 amplification by SISH. After a median follow-up of 13.2 months (range, 1.4-78.1 months), median progression-free survival (PFS) was significantly different according to HER2 status: 3.1 months in patients with HER2 amplification compared with 5.6 months in those with non-amplified HER2 (hazard ratio, 2.73; 95% confidence interval, 1.18-6.31; P = .019). Overall survival (OS) was not significantly different between groups, although there was a tendency towards shorter OS in patients with HER2-amplified tumors (hazard ratio, 1.31; 95% confidence interval, 0.61-2.82; 10.1 vs. 13.5 months; P = .488). Conclusions HER2 amplification is predictive of shorter PFS after cetuximab treatment in patients with mCRC harboring wild-type RAS and BRAF. Further study is warranted for this patient population.

Original languageEnglish
Pages (from-to)e147-e152
JournalClinical Colorectal Cancer
Volume16
Issue number3
DOIs
StatePublished - Sep 2017

Keywords

  • Chemotherapy
  • HER2 copy-number
  • Resistant
  • Survival
  • Target agent

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