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Poster display session

3969 - Comparison of cytotoxic backbones for first line trastuzumab-containing regimens in HER2-positive advanced esophagogastric cancer: A meta-analysis.


09 Sep 2017


Poster display session


Cytotoxic Therapy;  Oesophageal Cancer;  Gastric Cancer


Emil ter Veer


Annals of Oncology (2017) 28 (suppl_5): v209-v268. 10.1093/annonc/mdx369


E. ter Veer1, A. Creemers2, L. de Waal2, M.G.H. van Oijen2, H.W.M. van Laarhoven2

Author affiliations

  • 1 Department Of Medical Oncology, Academic Medical Center (AMC), 1105AZ - Amsterdam/NL
  • 2 Department Of Medical Oncology, Academic Medical Centre, University of Amsterdam, Amsterdam/NL


Abstract 3969


According to the ToGA study, trastuzumab plus cisplatin and capecitabine/5-fluorouracil (5-FU) is standard first-line treatment for HER2+ advanced esophagogastric cancer. However, optimality of this cytotoxic backbone is questioned. We examined the relative efficacy and safety of alternative trastuzumab-based cytotoxic backbone regimens compared to standard ToGA using meta-analysis.


Medline, EMBASE, CENTRAL and ASCO and ESMO were searched up to March 2017 for studies investigating alternative first-line trastuzumab-based regimens for patients with HER2+ esophagogastric cancer, with protein expression IHC3+ or IHC2+ and gene amplification by in situ hybridisation (ISH+). We compared overall survival (OS) of alternative trastuzumab-based regimens to trastuzumab plus cisplatin and capecitabine/5-FU of the ToGA trial IHC3+ or IHC2+/ISH+ subgroup. Hazard ratios (HR) and 95% confidence intervals (95%CI) were calculated by extraction of published Kaplan-Meier curves. Incidence counts and toxicity sample sizes were extracted for grade 1-2 and grade 3-4 adverse events and compared using single arm proportion meta-analysis.


We included 15 studies (557 patients). For doublet backbone regimens, OS was significantly longer with trastuzumab plus oxaliplatin and capecitabine/5-FU compared to the ToGA regimen (median OS 20.7 vs 16.0 months, HR 0.75, 95%CI 0.59-0.99) and showed a more convenient toxicity profile. The doublet backbone trastuzumab plus cisplatin and S-1 showed no significant difference in OS compared to the ToGA regimen, but had a different toxicity profile, including less grade 1-2 hand-foot syndrome. Trastuzumab plus singlet backbone cisplatin or capecitabine had a significantly worse survival compared to the ToGA regimen and were more toxic. Trastuzumab with triplet cytotoxic backbones or with bevacizumab and doublet cytotoxic backbone had no survival benefit and were generally more toxic compared to ToGA.


Trastuzumab plus a doublet cytotoxic backbone containing oxaliplatin is preferable compared to the conventional ToGA regimen with cisplatin. S-1 can substitute capecitabine or 5-FU when specific toxicities are encountered.

Clinical trial identification

Not applicable

Legal entity responsible for the study





M.G.H. van Oijen: Unrestricted research grants from Bayer, Lilly, Merck Serono, and Roche. H.W.M. van Laarhoven: Consultant for Celgene, Lilly, and Nordic. Unrestricted research funding from Bayer, BMS, Celgene, Lilly, Merck Serono, MSD, Nordic, and Roche. All other authors have declared no conflicts of interest.

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