Prognostic significance of human epidermal growth factor-2 (HER2) in advanced gastric cancer: A U.S. and European international collaborative analysis.

Shah, Mazhar Ali; Janjigian, Y. Y.; Pauligk, Claudia; Werner, Dominique; Dp, Kelsen; Jaeger, Erich B.; Altmannsberger, Hans-Michael; Robinson, Emily; Tang, Liang; Barbashina, Violetta; Al-Batran, S.

doi:10.1200/jco.2011.29.15_suppl.4014

Cited by 14 publications

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“…The same conclusion was reached in a US and European collaborative analysis recently presented by Shah et al at the ASCO 2011 meeting 10. However, in the subgroup analysis based on tumour histology and HER2 status, only HER2 amplification determined by means of dc-SISH was deemed to be of prognostic value for intestinal type patients.…”

Section: Discussionsupporting

confidence: 62%

HER2/neutesting for anti-HER2-based therapies in patients with unresectable and/or metastatic gastric cancer

et al. 2012

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AimTo study the HER2 gene amplification or overexpression in patients with advanced gastric cancer (GC) and their association with patient characteristics and patient survival.Patients and methodsTumour tissue samples from 148 patients with advanced GC were studied for HER2 by immunohistochemistry (IHC), fluorescence in situ hybridisation (FISH) and dual colour silver enhanced in situ hybridisation (dc-SISH) methods. Clinicopathological data from all patients were collected. Progression free survival and overall survival were also analysed.ResultsMean age was 67 (33–83) years; 75% were male subjects, and 51% had intestinal histological type. HER2+ rates were 10.1% (15/148) by IHC, 18.2% (27/148) by FISH+ or 21.6% (32/148) by dc-SISH+. There were significant differences in HER2+ rates according to histological type when FISH (intestinal, 23%; no intestinal, 4%; p<0.0001) or dc-SISH (intestinal, 26%; no intestinal, 6%; p<0.0001) amplification techniques were used. Median overall survival was significantly longer in HER2+ patients despite the determination technique used: IHC (21.4 vs 9.8 months, HR 0.42; p=0.005); FISH (19.6 vs 9.7 months, HR 0.49; p=0.007) or dc-SISH (19.6 vs 9.7 months, HR 0.53; p=0.009). Factors associated with favourable survival in the multivariate analysis were intestinal type and Her2+ determination by IHC, FISH or dc-SISH.ConclusionHER2 gene amplification is significantly associated with patient survival. HER2 gene amplification approaches might be an optimal HER2/neu testing strategy for the selection of HER2+ GC patients who are candidates to be treated with anti-HER2 therapies.

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Section: Discussionsupporting

confidence: 62%

HER2/neutesting for anti-HER2-based therapies in patients with unresectable and/or metastatic gastric cancer

et al. 2012

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“…Although initial studies in gastric cancer suggested a similarly negative impact on prognosis [Yonemura et al 1991], more recent studies have reported no significant prognostic effect [Shah et al 2011;Terashima et al 2011;Yoon et al 2011].…”

Section: Prognostic Effect Of Her-2 Overexpression and Amplificationmentioning

confidence: 99%

Trastuzumab: a novel standard option for patients with HER-2-positive advanced gastric or gastro-oesophageal junction cancer

Okines

Cunningham

2012

Therap Adv Gastroenterol

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Abstract:The human epidermal receptor-2 (HER-2) is amplified in up to 25% of patients with gastroesophageal adenocarcinomas. Although the presence of this amplification does not appear to confer a poor prognosis, it provides a valuable novel therapeutic target for this group of patients. Trastuzumab is a fully humanized monoclonal antibody directed at HER-2 which binds the external domain of the receptor and exerts its action via a combination of antibodydependent cytotoxicity, reduced shedding of the extracellular domain, inhibition of dimerization and possibly receptor downregulation. The ToGA trial was an international multicentre randomized phase III study which evaluated the addition of trastuzumab to a cisplatin plus fluoropyrimidine chemotherapy doublet in 594 patients with HER-2-positive advanced gastric or oesophagogastric junction adenocarcinoma. The combination of the antibody with chemotherapy significantly improved response rate, median progression-free survival and median overall survival without additional toxicity or adversely affecting quality of life. Accordingly, trastuzumab plus chemotherapy is now a standard first-line treatment option for patients with advanced HER-2-positive gastroesophageal cancer. Unfortunately, many patients with HER-2-positive cancer exhibit primary resistance to trastuzumab and the remainder will acquire resistance to the antibody; therefore, urgent investigation into novel agents which may circumvent resistance mechanisms is warranted. Small molecule inhibitors of HER-2, which commonly also target other members of the HER family of receptors, such as EGFR and HER-3, are currently undergoing evaluation in gastroesophageal cancer as first-line alternatives to trastuzumab and second-line salvage treatments for trastuzumab-resistant disease. Extrapolating the successful use of trastuzumab in the advanced disease setting, clinical trials are underway to assess the role of this antibody in the perioperative and adjuvant settings, where it is hoped that it will have a meaningful impact upon the currently poor survival rates.

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“…The incidence of HER2 overexpression in gastric cancer is approaching 15%‐25% . Although HER2 may be correlated to a poor prognosis, HER2 positivity is no longer considered a poor prognostic factor . In the ToGA study, T‐mab was found to improve the median OS when combined with XP or cisplatin/5‐FU (13.5 months) in comparison with XP or CF alone (11.1 months) .…”

Section: Discussionmentioning

confidence: 99%

A remarkable clinical response in advanced gastric cancer treated with trastuzumab plus capecitabine combination chemotherapy: A report of two cases

Nakamura

Kinami

Fujii

et al. 2019

Clinical Case Reports

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Prognostic significance of human epidermal growth factor-2 (HER2) in advanced gastric cancer: A U.S. and European international collaborative analysis.

Cited by 14 publications

References 0 publications

HER2/neutesting for anti-HER2-based therapies in patients with unresectable and/or metastatic gastric cancer

HER2/neutesting for anti-HER2-based therapies in patients with unresectable and/or metastatic gastric cancer

Trastuzumab: a novel standard option for patients with HER-2-positive advanced gastric or gastro-oesophageal junction cancer

A remarkable clinical response in advanced gastric cancer treated with trastuzumab plus capecitabine combination chemotherapy: A report of two cases

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