What is the role of trastuzumab in treatment of advanced unresectable gastric cancer?

Updated: Feb 23, 2021
  • Author: Elwyn C Cabebe, MD; Chief Editor: N Joseph Espat, MD, MS, FACS  more...
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Overexpression of human epidermal growth factor receptor 2 (HER2) is a significant negative prognostic factor for gastric cancer. In the international ToGA trial (trastuzumab with chemotherapy in HER2-positive advanced gastric cancer), about 22% of patients with advanced gastric cancer were found to have tumors that overexpressed HER2. In this phase III trial, 594 patients with HER2-positive advanced gastric cancer were randomized to receive standard chemotherapy alone or chemotherapy plus trastuzumab (Herceptin). Overall survival with trastuzumab was 13.8 months, compared with 11.1 months in the chemotherapy group (hazard ratio [HR], 0.74, P = 0.0046). [59]

Although modest, this 2.7-month improvement in overall survival is clinically meaningful in this group of patients, who have a poor prognosis. In addition to the impact on overall survival, trastuzumab improved all of the secondary end points, including progression-free survival (increased from 5.2 mo to 6.7 mo; P = 0.002) and overall response rate (increased from 34.5% to 47%; P = 0.0017).

Trastuzumab was approved in 2010 for the treatment of HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma. It is administered in combination with cisplatin and capecitabine or 5-FU in patients who have not received prior treatment for metastatic disease. The trastuzumab dose consists of an initial cycle of 8 mg/kg intravenously (IV) infused over 90 minutes, followed by subsequent cycles of 6 mg/kg IV infused over 30-90 minutes every 3 weeks. Treatment is continued until the disease progresses.

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