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J Clin Oncol. 2013 Dec 10;31(35):4445-52. doi: 10.1200/JCO.2013.48.9070. Epub 2013 Oct 14.

Level of HER2 gene amplification predicts response and overall survival in HER2-positive advanced gastric cancer treated with trastuzumab.

Author information

1
Carlos Gomez-Martin, Elena Garralda, and Manuel Hidalgo, Spanish National Cancer Research Centre; Carlos Gomez-Martin, Jose Carlos Plaza, Fernando Lopez-Rios, and Manuel Hidalgo, Laboratorio Dianas Terapeuticas, Cenro Integral Oncologico Clara Campal, Hospital Universitario Sanchinarro; Federico Rojo and Ana Leon, Fundacion Jimenez Diaz, Madrid; Pilar Sanz-Moncasi, Hospital Royo-Villanova; Roberto Pazo-Cid and Elena del Valle, Hospital Universitario Miguel Servet, Zaragoza; Antonieta Salud and Felipe Vilardell, Hospital Universitario Arnau de Vilanova, Lérida; Francesc Pons, Mar Iglesias, and Clara Montagut, Hospital de Mar; Maria Alsina and Stefania Landolfi, Hospital Universitari Vall d'Hebrón; M. Carmen Galan and M. Jose Paulés, Instituto Catalan de Oncologia; Miriam Cuatrecasas and Laura Visa, Hospital Clinic Universitari, Barcelona; Paula Fonseca and Soledad Fernandez, Hospital Universitario Central de Asturias, Oviedo; Fernando Rivera and Marta Mayorga, Hospital Universitario Marques de Valdecilla, Santander, Spain.

Abstract

PURPOSE:

Previous studies have highlighted the importance of an appropriate human epidermal growth factor receptor 2 (HER2) evaluation for the proper identification of patients eligible for treatment with anti-HER2 targeted therapies. Today, the relationship remains unclear between the level of HER2 amplification and the outcome of HER2-positive gastric cancer treated with first-line chemotherapy with trastuzumab. The aim of this study was to determine whether the level of HER2 gene amplification determined by the HER2/CEP17 ratio and HER2 gene copy number could significantly predict some benefit in overall survival and response to therapy in advanced gastric cancer treated with trastuzumab-based chemotherapy.

PATIENTS AND METHODS:

Ninety patients with metastatic gastric cancer treated with first-line trastuzumab-based chemotherapy were studied. The optimal cutoff values for HER2/CEP17 ratio and HER2 gene copy number (GCN) for discriminating positive results in terms of response and prolonged survival were determined using receiver operating characteristic curves analyses.

RESULTS:

In this study, a median HER2/CEP17 ratio of 6.11 (95% CI, 2.27 to 21.90) and a median HER2 gene copy number of 11.90 (95% CI, 3.30 to 43.80) were found. A mean HER2/CEP17 ratio of 4.7 was identified as the optimal cutoff value discriminating sensitive and refractory patients (P = .005). Similarly, the optimal cutoff for predicting survival longer than 12 months was 4.45 (P = .005), and for survival longer than 16 months was 5.15 (P = .004). For HER2 GCN, the optimal cutoff values were 9.4, 10.0, and 9.5, respectively (P = .02).

CONCLUSION:

The level of HER2 gene amplification significantly predicts sensitivity to therapy and overall survival in advanced gastric cancer treated with trastuzumab-based chemotherapy.

PMID:
24127447
DOI:
10.1200/JCO.2013.48.9070
[Indexed for MEDLINE]

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