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Upper GI: Gastric HER2-positive metastatic disease (ToGA)

Free question published 22 October 2026

Upper GIGastric HER2-positive metastatic disease (ToGA)

A 64-year-old man has newly diagnosed metastatic gastric adenocarcinoma with liver metastases. Immunohistochemistry shows HER2 3+ (confirmed HER2-positive). He has WHO performance status 1 and adequate cardiac function. Which first-line systemic regimen should be offered?

  1. ATrastuzumab in combination with cisplatin and a fluoropyrimidine
  2. BFLOT chemotherapy
  3. CEpirubicin, cisplatin and capecitabine (ECX) alone
  4. DNivolumab monotherapy
  5. ECisplatin and a fluoropyrimidine (capecitabine or 5-fluorouracil) alone

Why A is correct

The ToGA trial showed that adding trastuzumab to cisplatin plus a fluoropyrimidine improved median overall survival to 13.8 versus 11.1 months (HR 0.74; p=0.0046) in HER2-positive advanced gastric or gastro-oesophageal junction cancer, establishing trastuzumab-chemotherapy as a standard first-line option. NICE NG83 recommends trastuzumab with cisplatin and capecitabine or 5-fluorouracil for HER2-positive metastatic disease.

And why the others are not

  • BFLOT is a perioperative regimen for resectable disease, not the standard first-line approach for HER2-positive metastatic gastric cancer.
  • CECX alone omits the HER2-directed trastuzumab that drove the survival benefit in ToGA.
  • DNivolumab monotherapy is not the first-line standard here; the HER2-positive status mandates trastuzumab-based therapy.
  • EChemotherapy alone omits the HER2-directed antibody that improved survival in this HER2-positive patient.

Source ToGA - Trastuzumab plus chemotherapy in HER2-positive advanced gastric or gastro-oesophageal junction cancer — Bang YJ, Van Cutsem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376(9742):687-697.

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