HER2 in high-risk rectal cancer patients treated in EXPERT-C, a randomized phase II trial of neoadjuvant capecitabine and oxaliplatin (CAPOX) and chemoradiotherapy (CRT) with or without cetuximab.

F. Sclafani, A. Roy, D. Cunningham, A. Wotherspoon, C. Peckitt, D. Gonzalez de Castro, J. Tabernero, B. Glimelius, A. Cervantes, Z. Eltahir, J. Oates, I. Chau

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

BACKGROUND: HER2 is an established therapeutic target in breast and gastric cancers. The role of HER2 in rectal cancer is unclear, as conflicting data on the prevalence of HER2 expression in this disease have been reported. We evaluated the prevalence of HER2 and its impact on the outcome of high-risk rectal cancer patients treated with neoadjuvant CAPOX and CRT±cetuximab in the EXPERT-C trial. PATIENTS AND METHODS: Eligible patients with available tumour tissue for HER2 analysis were included. HER2 expression was determined by immunohistochemistry (IHC) in pre-treatment biopsies and/or surgical specimens (score 0-3+). Immunostaining was scored according to the consensus panel recommendations on HER2 scoring for gastric cancer. Tumours with equivocal IHC result (2+) were tested for HER2 amplification by D-ISH. Tumours with IHC 3+ or D-ISH ratio ≥2.0 were classified as HER2+. The impact of HER2 on primary and secondary end points of the study was analysed. RESULTS: Of 164 eligible study patients, 104 (63%) biopsy and 114 (69%) surgical specimens were available for analysis. Only 3 of 104 (2.9%) and 3 of 114 (2.6%) were HER2+, respectively. In 77 patients with paired specimens, concordance for HER2 status was found in 74 (96%). Overall, 141 patients were assessable for HER2 and 6 out of 141 (4.3%) had HER2 overexpression and/or amplification. The median follow-up was 58.6 months. HER2 was not associated with a difference in the outcome for any of the study end points, including in the subset of 90 KRAS/BRAF wild-type patients treated±cetuximab. CONCLUSIONS: Based on the low prevalence of expression as recorded in the EXPERT-C trial, HER2 does not appear to represent a useful therapeutic target in high-risk rectal cancer. However, the role of HER2 as a potential predictive biomarker of resistance to anti-EGFR-based treatments and a therapeutic target in anti-EGFR refractory metastatic colorectal cancer (CRC) warrants further investigation. TRIAL REGISTRATION: ISRCTN Register: 99828560.
Original languageEnglish
Pages (from-to)3123-3128
Number of pages6
JournalAnnals of Oncology
Volume24
Issue number12
DOIs
Publication statusPublished - Dec 2013

Keywords

  • HER2
  • biomarker
  • cetuximab
  • chemoradiotherapy
  • neoadjuvant chemotherapy
  • rectal cancer
  • Adenocarcinoma
  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols
  • Capecitabine
  • Cetuximab
  • Chemoradiotherapy
  • Chemotherapy, Adjuvant
  • Deoxycytidine
  • Disease-Free Survival
  • Female
  • Fluorouracil
  • Humans
  • Male
  • Middle Aged
  • Neoadjuvant Therapy
  • Organoplatinum Compounds
  • Proportional Hazards Models
  • Receptor, ErbB-2
  • Rectal Neoplasms
  • Retrospective Studies
  • Single-Blind Method
  • Treatment Outcome

Fingerprint Dive into the research topics of 'HER2 in high-risk rectal cancer patients treated in EXPERT-C, a randomized phase II trial of neoadjuvant capecitabine and oxaliplatin (CAPOX) and chemoradiotherapy (CRT) with or without cetuximab.'. Together they form a unique fingerprint.

  • Cite this