Treatment of Advanced or Metastatic Gastric Cancer with HER2 Overexpression (HER2 IHC 3+)

This protocol covers patients with advanced or metastatic gastric cancer whose tumours show confirmed HER2 overexpression. HER2 testing status directly determines the applicable treatment pathway in this clinical setting.

Clinical Scenario

Advanced or metastatic gastric cancer with HER2 overexpression — defined as HER2 IHC 3+, or HER2 IHC 2+ with FISH-positive confirmation. Accurate HER2 testing is the key criterion for patient selection in this population.

Treatment Approach (Partial Overview)

Second-line management in this population involves antiangiogenic-based regimens combined with chemotherapy, with alternative single-agent chemotherapy options available when certain agents cannot be used. An antibody-drug conjugate may be considered in select cases. The complete regimen, full range of options, and clinical sequencing are detailed in the full protocol.

Instant Access to Structured Evidence-Based Regimens

References

Adding trastuzumab to ChT is recommended for patients with HER2-overexpressing (HER2 IHC 3+ or IHC 2+/FISH positive) gastric cancer, based on the phase III ToGA study.
Ramucirumab–paclitaxel is recommended for second-line treatment of gastric cancer [I, A; ESMO-MCBS v1.1 score: 2]. Ramucirumab monotherapy is also an option [I, B; ESMO-MCBS v1.1 score: 1].
Where ramucirumab is not available, paclitaxel, docetaxel or irinotecan monotherapy [I, A] or FOLFIRI [II, B] are recommended.
Treatment with trastuzumab is not recommended after first-line therapy in HER2-positive advanced gastric cancer [I, D], but trastuzumab deruxtecan may be considered [II, B; ESMO-MCBS v1.1 score: 4; FDA approved, not EMA approved].

DOI: 10.1016/j.annonc.2022.07.004

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