Researchers involved in an international randomized Phase III clinical trial have reported that treatment with Herceptin® (trastuzumab) improves survival among patients with HER2-positive, advanced and inoperable stomach cancer. These results were presented at the Joint ECCO 15 – 34^th ESMO Multidisciplinary Congress in Berlin, September 20-24, 2009.

Herceptin is a targeted therapy that has made important contributions to improved outcomes among women with HER2-positive breast cancer. The HER2 pathway is a biological pathway involved in cellular replication and growth. Approximately 20-25% of breast cancers overexpress the HER2 protein and are referred to as HER2-positive. Herceptin targets and blocks the HER2-protein and is used for the treatment of both early-stage and more advanced HER2-positive breast cancer.

HER2 is also overexpressed in some patients with stomach cancer. To evaluate the safety and efficacy of Herceptin among patients with HER2-positive, advanced and inoperable stomach cancer, researchers conducted an international Phase III clinical trial study among 594 patients.

Half the patients were treated with chemotherapy alone, and half the patients were treated with chemotherapy plus Herceptin. Chemotherapy consisted of a fluoropyrimidine (Xeloda® [capecitabine] or 5-FU) and cisplatin.

• Overall survival was 13.8 months among patients treated with chemotherapy plus Herceptin compared with 11.1 months among patients treated with chemotherapy alone.
• Median progression-free survival was 6.7 months for patients receiving chemotherapy plus Herceptin compared with 5.5 months for patients treated with chemotherapy alone.
• Median time to tumor progression was 7.1 months for patients receiving chemotherapy plus Herceptin compared with 5.6 months for patients treated with chemotherapy alone.
• Overall response rate was 47.3% for patients receiving chemotherapy plus Herceptin compared with 34.5% for patients receiving chemotherapy alone.
• Median duration of response was 6.8 months for patients receiving chemotherapy plus Herceptin compared with 4.8 months for patients receiving chemotherapy alone.
• Clinical benefit was achieved in 78.9% of patients receiving chemotherapy plus Herceptin compared with 69% for patients receiving chemotherapy alone.
• Toxicities of the two arms were similar, except for a higher frequency of diarrhea in patients receiving Herceptin.
• Patients whose tumors had the highest levels of HER2 appeared to derive the most benefit from Herceptin. Among patients with particularly high levels of HER2, overall survival was 16 months for those treated with chemotherapy plus Herceptin compared with 11.8 months for those treated with chemotherapy alone.

Comments: These results suggest that Herceptin improves survival among patients with HER-positive, advanced stomach cancer. These authors suggest that this “sets a new standard in patients with HER2-positive gastric cancer.”

Reference: Van Cutsem E, Kang YK, Shen L et al. Trastuzumab added to standard chemotherapy (CT) as first-line treatment in human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (GC): efficacy and safety results from the Phase III ToGA trial. European Journal of Cancer Supplements, Vol. 7, No 3, September 2009, Page 7, Abstract 7BA.