Assessment of her2 gene amplification in adenocarcinomas of the stomach or gastroesophageal junction in the int-0116/swog9008 clinical trial

M. A. Gordon, H. M. Gundacker, J. Benedetti, J. S. Macdonald, J. C. Baranda, W. J. Levin, Charles Blanke, W. Elatre, P. Weng, J. Y. Zhou, H. J. Lenz, M. F. Press

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Abstract

Background: Trastuzumab has been approved for patients with human epidermal growth factor receptor 2 (HER2)- positive metastatic gastric carcinoma; however, relatively little is known about the role of HER2 in the natural history of this disease. Patients and methods: Patients enrolled in the INT-0116/SWOG9008 phase III gastric cancer clinical trial with available tissue specimens were retrospectively evaluated for HER2 gene amplification by FISH and overexpression by immunohistochemistry (IHC). The original trial was designed to evaluate the benefit of postoperative chemoradiation compared with surgery alone. Results: HER2 gene amplification rate by FISH was 10.9% among 258 patients evaluated. HER2 overexpression rate by IHC was 12.2% among 148 patients evaluated, with 90% agreement between FISH and IHC. There was a significant interaction between HER2 amplification and treatment with respect to both disease-free survival (DFS) (P = 0.020) and overall survival (OS) (P = 0.034). Among patients with HER2-non-amplified cancers, treated patients had a median OS of 44 months compared with 24 months in the surgery-only arm (P = 0.003). Among patients with HER2- amplified cancers, there was no significant difference in survival based on treatment arm. HER2 status was not a prognostic marker among patients who received no postoperative chemoradiation. Conclusion: Patients lacking HER2 amplification benefited from treatment as indicated by both DFS and OS. Clinical trial: INT-0116/SWOG9008 phase III.

Original languageEnglish (US)
Article numbermdt106
Pages (from-to)1754-1761
Number of pages8
JournalAnnals of Oncology
Volume24
Issue number7
DOIs
StatePublished - Jul 2013

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Esophagogastric Junction
Gene Amplification
Stomach
Adenocarcinoma
Clinical Trials
erbB-1 Genes
Survival
Immunohistochemistry
Disease-Free Survival
human ERBB2 protein
Stomach Neoplasms
Neoplasms
Therapeutics
Carcinoma

Keywords

  • 5Fu chemotherapy
  • Fish
  • Gastric cancer
  • Her2
  • Immunohistochemistry
  • Radiation therapy

ASJC Scopus subject areas

  • Oncology
  • Hematology

Cite this

Gordon, M. A., Gundacker, H. M., Benedetti, J., Macdonald, J. S., Baranda, J. C., Levin, W. J., ... Press, M. F. (2013). Assessment of her2 gene amplification in adenocarcinomas of the stomach or gastroesophageal junction in the int-0116/swog9008 clinical trial. Annals of Oncology, 24(7), 1754-1761. [mdt106]. https://doi.org/10.1093/annonc/mdt106

Assessment of her2 gene amplification in adenocarcinomas of the stomach or gastroesophageal junction in the int-0116/swog9008 clinical trial. / Gordon, M. A.; Gundacker, H. M.; Benedetti, J.; Macdonald, J. S.; Baranda, J. C.; Levin, W. J.; Blanke, Charles; Elatre, W.; Weng, P.; Zhou, J. Y.; Lenz, H. J.; Press, M. F.

In: Annals of Oncology, Vol. 24, No. 7, mdt106, 07.2013, p. 1754-1761.

Research output: Contribution to journalArticle

Gordon, MA, Gundacker, HM, Benedetti, J, Macdonald, JS, Baranda, JC, Levin, WJ, Blanke, C, Elatre, W, Weng, P, Zhou, JY, Lenz, HJ & Press, MF 2013, 'Assessment of her2 gene amplification in adenocarcinomas of the stomach or gastroesophageal junction in the int-0116/swog9008 clinical trial', Annals of Oncology, vol. 24, no. 7, mdt106, pp. 1754-1761. https://doi.org/10.1093/annonc/mdt106
Gordon, M. A. ; Gundacker, H. M. ; Benedetti, J. ; Macdonald, J. S. ; Baranda, J. C. ; Levin, W. J. ; Blanke, Charles ; Elatre, W. ; Weng, P. ; Zhou, J. Y. ; Lenz, H. J. ; Press, M. F. / Assessment of her2 gene amplification in adenocarcinomas of the stomach or gastroesophageal junction in the int-0116/swog9008 clinical trial. In: Annals of Oncology. 2013 ; Vol. 24, No. 7. pp. 1754-1761.
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abstract = "Background: Trastuzumab has been approved for patients with human epidermal growth factor receptor 2 (HER2)- positive metastatic gastric carcinoma; however, relatively little is known about the role of HER2 in the natural history of this disease. Patients and methods: Patients enrolled in the INT-0116/SWOG9008 phase III gastric cancer clinical trial with available tissue specimens were retrospectively evaluated for HER2 gene amplification by FISH and overexpression by immunohistochemistry (IHC). The original trial was designed to evaluate the benefit of postoperative chemoradiation compared with surgery alone. Results: HER2 gene amplification rate by FISH was 10.9{\%} among 258 patients evaluated. HER2 overexpression rate by IHC was 12.2{\%} among 148 patients evaluated, with 90{\%} agreement between FISH and IHC. There was a significant interaction between HER2 amplification and treatment with respect to both disease-free survival (DFS) (P = 0.020) and overall survival (OS) (P = 0.034). Among patients with HER2-non-amplified cancers, treated patients had a median OS of 44 months compared with 24 months in the surgery-only arm (P = 0.003). Among patients with HER2- amplified cancers, there was no significant difference in survival based on treatment arm. HER2 status was not a prognostic marker among patients who received no postoperative chemoradiation. Conclusion: Patients lacking HER2 amplification benefited from treatment as indicated by both DFS and OS. Clinical trial: INT-0116/SWOG9008 phase III.",
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AU - Gundacker, H. M.

AU - Benedetti, J.

AU - Macdonald, J. S.

AU - Baranda, J. C.

AU - Levin, W. J.

AU - Blanke, Charles

AU - Elatre, W.

AU - Weng, P.

AU - Zhou, J. Y.

AU - Lenz, H. J.

AU - Press, M. F.

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AB - Background: Trastuzumab has been approved for patients with human epidermal growth factor receptor 2 (HER2)- positive metastatic gastric carcinoma; however, relatively little is known about the role of HER2 in the natural history of this disease. Patients and methods: Patients enrolled in the INT-0116/SWOG9008 phase III gastric cancer clinical trial with available tissue specimens were retrospectively evaluated for HER2 gene amplification by FISH and overexpression by immunohistochemistry (IHC). The original trial was designed to evaluate the benefit of postoperative chemoradiation compared with surgery alone. Results: HER2 gene amplification rate by FISH was 10.9% among 258 patients evaluated. HER2 overexpression rate by IHC was 12.2% among 148 patients evaluated, with 90% agreement between FISH and IHC. There was a significant interaction between HER2 amplification and treatment with respect to both disease-free survival (DFS) (P = 0.020) and overall survival (OS) (P = 0.034). Among patients with HER2-non-amplified cancers, treated patients had a median OS of 44 months compared with 24 months in the surgery-only arm (P = 0.003). Among patients with HER2- amplified cancers, there was no significant difference in survival based on treatment arm. HER2 status was not a prognostic marker among patients who received no postoperative chemoradiation. Conclusion: Patients lacking HER2 amplification benefited from treatment as indicated by both DFS and OS. Clinical trial: INT-0116/SWOG9008 phase III.

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