Trastuzumab: a review of its use in HER2-positive advanced gastric cancer.
Trastuzumab (Herceptin(®)) is a humanized monoclonal antibody that binds selectively to human epidermal growth factor 2 (HER2), interfering with its downstream cancer-promoting effects. This article focuses on the efficacy and tolerability of trastuzumab in HER2-positive advanced gastric cancer. The potential of trastuzumab as a cytotoxic for use in gastric cancer was confirmed by in vitro studies in HER2-positive gastric cancer cell lines and gastric cancer xenograft models. In a randomized, controlled, open-label, multinational trial in patients with HER2-positive advanced gastric cancer, trastuzumab plus chemotherapy (cisplatin plus capecitabine or 5-fluorouracil) was significantly more efficacious than chemotherapy alone, in terms of a longer median overall survival (13.8 vs. 11.1 months in the chemotherapy alone group) [primary endpoint], a longer median progression-free survival, and a higher response rate. Trastuzumab was efficacious across patient subgroups, although stronger effects were observed in a subgroup with high HER2 overexpression (immunohistochemistry 2+/fluorescence in-situ hybridization positive or immunohistochemistry 3+). There was a slightly higher tolerability burden in the trastuzumab plus chemotherapy group than with chemotherapy alone, based on small between-group numerical differences in rates of common gastrointestinal and general adverse events. Most individual adverse events reported in this trial were at a grade 1 or 2 level of severity. However, in both treatment groups approximately half of the haematological adverse were at a grade 3 or 4 level of severity, with no marked between-group differences. Trastuzumab in combination with cisplatin and a fluoropyrimidine is an effective regimen for patients with HER2-positive advanced gastric cancer, has acceptable tolerability and represents an important advance in the treatment of gastric cancer.
Adis, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, North Shore, 0754, Auckland, New Zealand, demail@springer.com.
Mark
M
Sanford
D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D018572:Disease-Free Survival; D006801:Humans; D015337:Multicenter Studies as Topic; D016032:Randomized Controlled Trials as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D000068878:Trastuzumab
D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human