FDA approves trastuzumab to treat HER2-overexpressing metastatic gastric or gastroesophageal cancer

On October 20, 2010, FDA approved trastuzumab (Herceptin, Genentech) for use in combination with cisplatin and capecitabine or 5-fluorouracil to treat patients with human epidermal growth factor receptor 2 (HER2)-overexpressing (also called HER2-positive) metastatic gastric or gastroesophageal junction cancer who have not received prior treatment for metastatic disease. Earlier this year, the European Medicines Agency (EMA) approved trastuzumab for a similar gastric cancer indication. These regulatory agencies’ decisions to approve trastuzumab for this new indication (previously approved for the treatment of HER2-overexpressing breast cancer) was largely based upon the results of the “Trastuzumab for Gastric Cancer” or ToGA trial, which was published in the August 28, 2010 Lancet. 

In ToGA, researchers randomized in an open-label fashion 594 (584 analyzed in primary analysis) patients with metastatic HER2-overexpressing gastric or gastroesophageal junction cancer to receive chemotherapy with cisplatin plus capecitabine or 5-fluorouracil either alone (n=290) or in combination with trastuzumab (n=294) (8 mg/kg on day 1 of the first cycle, followed by 6 mg/kg every 3 weeks until disease progression, unacceptable toxicity, or withdrawal of consent). After a median follow-up of 18.6 months, the trial revealed that those receiving trastuzumab plus chemotherapy had a median overall survival of 13.8 months compared to 11.1 months for those assigned to chemotherapy alone, a 26% reduction in the death rate (HR=0.74; 95% CI, 0.60–0.91; P=.0046).

In response to ToGA results, the trial’s researchers noted,  “In recent years, the development of new treatments and combination chemotherapies for advanced gastric cancer has led to a steady increase in overall survival beyond the 3 to 5 months seen with best supportive care alone.” They continued, “Single-agent chemotherapies provided an incremental benefit, but the biggest advances have been seen with two-drug and three-drug combinations.”

Common adverse events seen in ToGA (depicted as trastuzumab plus chemotherapy vs chemotherapy alone) included nausea (67% vs 63%), vomiting (50% vs 46%), and neutropenia (53% vs 57%). Overall rates of severe adverse events were similar between treatment groups, as were cardiac-specific adverse events (occurring in 6% of patients in each treatment group). Thus trial researchers concluded, “The addition of trastuzumab to chemotherapy did not increase toxic effects associated with standard fluoropyrimidine-based and platinum-based chemotherapy.”

According to the American Cancer Society, an estimated 21,000 Americans will be diagnosed with gastric cancer and more than 10,500 will die from the disease in 2010.  

“Trastuzumab can be considered as a new standard option for patients with HER2-positive advanced gastric or gastroesophageal junction cancer when combined with a chemotherapy regimen consisting of capecitabine plus cisplatin or fluorouracil plus cisplatin,” concluded the ToGA trial researchers.