699P - HER2 status in advanced gastric carcinoma patients treated with trastuzumab

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Biomarkers
Gastric Cancer
Presenter Carlos Gómez-Martín
Authors C. Gómez-Martín1, J.C. Plaza2, E. Del Valle3, F. Pons Valladares4, P. Jimenez Fonseca5, A. Salud6, A. Leon7, F. Rivera8, E. Garralda1, F. Lopez-Rios2
  • 1Clinical Research Programme, Spanish National Cancer Research Center, 28029 - Madrid/ES
  • 2Laboratorio Dianas Terapeuticas, Hospital Universitario Madrid-Norte Sanchinarro, Madrid/ES
  • 3Pathology Department, Hospital Universitario Miguel servet, Zaragoza/ES
  • 4Medical Oncology, Hospital del Mar, Barcelona/ES
  • 5Servicio De Oncologia Medica, Hospital Universitario Central de Asturias, 33006 - Oviedo/ES
  • 6Medical Oncology, Hospital Universitario Arnau de Vilanova, Lerida/ES
  • 7Medical Oncology, Fundacion Jimenez Diaz, Madrid/ES
  • 8Medical Oncology, Hospital Universitario Marques de Valdecilla, Santander/ES

Abstract

Background

Trastuzumab (T) added to standard chemotherapy increases overall survival for HER2 positive advanced gastric carcinoma (AGC) patients. The approval of T by the EMA in AGC was linked to the determination of the HER2-status by immunohistochemistry (IHC), and hybridization was only permitted in the 2+ subgroup. Taking into consideration the previous highs and lows in breast carcinoma HER2 testing, we sought to evaluate the use of Dual Colour Silver-staining in situ Hybridization (dc-SISH) for selecting patients with AGC as candidates to anti-HER2 therapies.

Material and methods

Sixty-nine AGC patients meeting a previously set of specific inclusion criteria were included: previous treatment with Trastuzumab-based chemotherapy, adequate follow-up, available pathology data and suitable sample for molecular analyses. IHC results were determined by the Pathway anti HER2/neu (4B5) antibody in the fully automated platform BenchMark ULTRA® (Ventana Medical Systems, Inc, Tucson, AZ). Automated dc-SISH was performed on Ventana Benchmark XT (Ventana Medical Systems, Tucson, AZ). INFORM HER2 DNA Probe and INFORM Chromosome 17 Probe was visualized on the same slide following the manufacturer's protocols. Gene to CEN-17 ratio was calculated using the cut-off value of HER2/CEN-17 ratio ≥2 as amplified. IHC evaluation was performed according to published guidelines.

Results

All cases were amplified. Low polisomy was present in 4 cases. Heterogeneity was observed in 24 (34.78%) cases. A statistically significant relationship was found between IHC and dc-SISH results (p < 0.0001), with 94% of IHC 3+ expressing dc-SISH ratio >4. Median OS was 19.8 months (95% CI: 13.4 – 23.9 months) for the entire population. Mean OS was significantly longer in the group of patients with amplification ratio >4 (21.4 vs. 8.0 months, HR 0.41; p = 0.0087; CI95% 0.2126 – 0.8180). No differences were observed in OS according to IHC results when stratified in two groups (3+ vs 0/1 + 2+) (21.0 vs 10.9 months, HR 0.5288, CI95% 0.2469 – 1.1325, p = 0.0955).

Conclusions

Dc-SISH amplification ratio >4 predicts OS benefit in AGC patients treated with trastuzumab in this study. Characterization in a larger cohort of patients is ongoing.

Disclosure

All authors have declared no conflicts of interest.