22% of patients with advanced gastric cancer overexpress human epidermal growth-factor receptor 2 (HER2), and these patients had significantly improved overall survival when trastuzumab (Herceptin), a drug against this receptor, is added to chemotherapy when compared with chemotherapy alone. In a study presented in 2009 ASCO, the improvement in overall survival was 2.7 months, from 11.1 months in the chemotherapy group to 13.8 months in the trastuzumab group (hazard ratio, 0.74, P = .0046). Similar results were shown by ToGA, a large international Phase III trial investigating the benefit of Herceptin as the first therapy for patients with advanced and inoperable stomach cancer (first line).
This greatly increased and interest in Tykerb for gastric cancer which works in a similar way. Preclinical studies in gastric cancer have shown that the drug slows down the growth of HER2-positive gastric cancer cell lines, showing synergy with trastuzumab. This agent is under study alone and combinations. A recent study by Iqbal concluded that Lapatinib is well tolerated, with modest single-agent activity in advanced/metastatic gastric cancer patients.
There are several ongoing studies of Tykerb and gastric cancer, for example: LOGiC – Lapatinib Optimization Study in ErbB2 (HER2) Positive Gastric Cancer: A Phase III Global, Blinded Study Designed to Evaluate Clinical Endpoints and Safety of Chemotherapy Plus Lapatinib, NCT00680901. There is also the TYTAN trial investigating weekly paclitaxel plus or minus Tykerb in second-line therapy.
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