Effect of HER2 on prognosis and benefit from peri-operative chemotherapy in early oesophago-gastric adenocarcinoma in the MAGIC trial

• Published in: Annals of oncology Vol. 24; no. 5; pp. 1253 - 1261
• Main Authors: Okines, A.F.C., Thompson, L.C., Cunningham, D., Wotherspoon, A., Reis-Filho, J.S., Langley, R.E., Waddell, T.S., Noor, D., Eltahir, Z., Wong, R., Stenning, S.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.05.2013; Oxford University Press
• Subjects: adenocarcinoma; Adenocarcinoma - drug therapy; Adenocarcinoma - genetics; Adenocarcinoma - surgery; Adult; Aged; Aged, 80 and over; Antineoplastic agents; Antineoplastic Agents - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Biomarkers, Tumor - metabolism; Cisplatin - therapeutic use; Combined Modality Therapy; Epirubicin - therapeutic use; Esophageal Neoplasms - drug therapy; Esophageal Neoplasms - genetics; Esophageal Neoplasms - surgery; Female; Fluorouracil - therapeutic use; gastric; Gastroenterology. Liver. Pancreas. Abdomen; hER2; Humans; immunohistochemistry; in situ hybridisation; Male; Medical sciences; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); oesophageal; Perioperative Period; Pharmacology. Drug treatments; Prognosis; Receptor, ErbB-2 - genetics; Receptor, ErbB-2 - metabolism; Stomach Neoplasms - drug therapy; Stomach Neoplasms - genetics; Stomach Neoplasms - surgery; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; Young Adult; adenocarcinoma; in situ hybridisation; gastric; immunohistochemistry; oesophageal; hER2; Immunohistochemistry; Prognosis; erbB2 Gene; Stomach cancer; Clinical trial; Protooncogene; Gastric disease; Stomach; Digestive system; Malignant tumor; Stomach adenocarcinoma; Human Epidermal growth factor Receptor 2; Esophagus; Anatomic pathology; Chemotherapy; Treatment; C-Onc gene; Digestive diseases; Early; In situ hybridization; Cancer
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mds622

Perioperative epirubicin, cisplatin and fluorouracil (ECF) chemotherapy improves survival in operable oesophago-gastric cancer [Adjuvant Gastric Cancer Infusional Chemotherapy (MAGIC) trial HR 0.75 (0.6–0.93)]. HER2 amplification is reported to predict enhanced benefit from anthracyclines in breast cancer. We sought to define whether HER2 predicts benefit from ECF in oesophago-gastric cancer. Diagnostic biopsies and/or resection specimens were collected from 415 of 503 MAGIC trial patients (82.5%). HER2 was evaluated by immunohistochemistry (IHC) and brightfield dual in situ hybridisation (BDISH) in tissue microarrays. The prognostic and predictive impact of HER2 status was investigated. Concordance between HER2 over-expression (IHC3+) and amplification was 96%. Results of HER2 assessment in biopsy and resection specimens were concordant in 92.9% (145/156). HER2 positive rate (IHC3+, or IHC2+/BDISH positive) was 10.9% in the whole cohort and 10.4% in resection specimens. A further 4.0% of resections were IHC negative/BDISH positive. HER2 status was neither prognostic, nor (in pre-treatment biopsies) predicted enhanced benefit from chemotherapy [HER2 positive HR 0.74 (0.14–3.77); HER2 negative HR 0.58 (0.41–0.82), interaction P = 0.7]. However, the power of the predictive analysis was limited by the small number of HER2 positive pre-treatment biopsies. HER2 status is not an independent prognostic biomarker in early oesophago-gastric adenocarcinoma.