Phase II study to evaluate the efficacy of Trastuzumab in combination with Capecitabine and Oxaliplatin in first-line treatment of HER2-positive advanced gastric cancer: HERXO trial

Cancer Chemother Pharmacol. 2019 Jun;83(6):1175-1181. doi: 10.1007/s00280-019-03820-7. Epub 2019 Mar 29.


Purpose: The phase III ToGA trial established cisplatin, fluoropyrimidine and trastuzumab as the standard treatment in HER2-positive advanced gastric cancer (AGC). However, as demonstrated in HER2-negative AGC, oxaliplatin-based regimens could improve tolerance remaining effective. The aim of this trial was to explore the potential activity and safety of capecitabine, oxaliplatin (XELOX) and trastuzumab in patients with HER-2 positive advanced gastric cancer.

Methods: We conducted a multicentre, prospective, non-randomised, non-controlled, open-label and national (Spanish) phase II study. Patients with HER2-positive advanced gastric or gastro-oesophageal junction (EGJ) cancer received XELOX and trastuzumab as first-line treatment. Primary endpoint was objective tumour response rate (ORR).

Results: 45 patients from ten hospitals in Spain were included from September 2011 to December 2013. Median age was 65 years, 82.2% were male, 69% had gastric cancer and 31% had EGJ tumours. At a median follow-up of 13.7 months (7.1-20.9), the estimated median progression-free survival and overall survival were 7.1 (95% CI 5.5-8.7) and 13.8 months (95% CI 10.1-17.4), respectively, with 8.9%, 37.8% and 31.1% of patients achieving complete response, partial response and stable disease. Regarding safety, 44.4% of the patients had grade 3 or greater adverse events, being the most frequent diarrhoea (26.6%), fatigue (15.5%), nausea (20%) and vomiting (13.3%). Only two patients (4.4%) developed asymptomatic grade 2 left ventricle ejection fraction reduction.

Conclusions: XELOX-trastuzumab is a promising and effective therapy as first-line treatment for patients with HER2-positive AGC, with comparable results to the ones obtained with other "platinum-based" regimens. This scheme is feasible and tolerable with a low incidence of cardiac toxicity.

Keywords: Advanced gastric cancer; Capecitabine; HER2 positive; Oxaliplatin; Phase II study; Trastuzumab.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Capecitabine
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives*
  • Esophagogastric Junction / pathology*
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Fluorouracil / analogs & derivatives*
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Oxaloacetates
  • Progression-Free Survival
  • Prospective Studies
  • Receptor, ErbB-2 / metabolism
  • Spain
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / pathology
  • Survival Rate
  • Trastuzumab / administration & dosage
  • Treatment Outcome


  • Oxaloacetates
  • Deoxycytidine
  • Capecitabine
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Trastuzumab
  • Fluorouracil

Supplementary concepts