HER2-positive gastric cancer

Abstract

Human epidermal growth factor receptor 2 (HER2) is involved in the pathogenesis and poor outcomes of several types of cancer, including advanced gastric and gastroesophageal junction cancer. Molecular-targeted drugs, such as trastuzumab, which prolong overall survival and progression-free survival in HER2-positive breast cancer, may also be beneficial in patients with HER2-positive gastric cancer. Several studies have examined this possibility, such as the Trastuzumab for Gastric Cancer trial. In this context, the first part of this review provides an update on our knowledge of HER2 in breast and gastric cancer, including the detection and prognostic relevance of HER2 in gastric cancer. The second part of the review discusses the results of pivotal clinical trials that examined the potential for using trastuzumab to treat this disease. This section also summarizes the trials that have been conducted or that are underway to determine the optimal uses of trastuzumab in gastric cancer, including its use as monotherapy and continuation beyond disease progression. The final section discusses the future prospects of other anti-HER2 drugs, including lapatinib, trastuzumab emtansine, and pertuzumab, for the treatment of HER2-positive gastric cancer. The introduction of trastuzumab led to the establishment of a new disease entity, "HER2-positive gastric cancer," similar to HER2-positive breast cancer. It is expected that more anti-HER2 drugs will be developed and introduced into clinical practice to treat HER2-positive cancers, including gastric cancer.

Fig. 1

Median survival (a) and progression-free survival (b) in the ToGA trial [11]. HR hazard ratio, CI confidence interval. Reprinted with permission from Elsevier Ltd

Fig. 2

Results of the ToGA trial [11]. a Pre-planned exploratory and post hoc exploratory analyses of patients stratified by HER2 status. *n = 561; patients with no immunohistochemistry (IHC) data (n = 7) or IHC 3+ tumors with no fluorescence in situ hybridization (FISH) data (n = 16) were excluded from the analysis. ^† n = 577; patients with no IHC data were excluded from the analysis. b Overall survival in patients with higher HER2 expression (IHC 2+ and FISH-positive tumors or IHC 3+ tumors). HR hazard ratio, CI confidence interval. Reprinted with permission from Elsevier Ltd

Fig. 3

Number of cycles of combination drugs administered in individual patients enrolled in the ToGA trial [11] in the control (a) or trastuzumab (b) groups