Interim safety analysis from TYTAN: A phase III Asian study of lapatinib in combination with paclitaxel as second-line therapy in gastric cancer.

Abstract

4057 Background: The standard care for advanced gastric adenocarcinoma varies between Western and Asian countries. In patients with HER2-positive advanced gastric cancer, the anti-HER2 antibody trastuzumab recently showed a significant survival benefit in the first-line therapy (ASCO 2009). Second-line weekly paclitaxel has shown favorable response rates (14.3-40.0%) in patients with gastric cancer and is now used widely in Japan and well accepted in other Asian countries. Successful data with lapatinib, a dual inhibitor of HER2 and EGFR, in combination with paclitaxel have been reported from several breast cancer trials. In vitro, lapatinib showed an anti-proliferative activity on N87, a HER2-positive gastric cancer cell line. Based on these backgrounds, we planned TYTAN (lapatinib [Tykerb] with paclitaxel [Taxol] in Asian ErbB2+[HER2+] Gastric Cancer Study), an open-label, randomized phase III study of second-line therapy with paclitaxel with or without lapatinib in patients with HER2-positive gastric cancer. Methods: Patients with advanced gastric cancer who showed a progression during the first-line therapy were screened for HER2 status by fluorescence in situ hybridization. Then, HER2-amplified patients were randomized to either weekly paclitaxel (80 mg/m2) alone or with daily lapatinib (1,500 mg/day). The primary endpoint is overall survival with a required sample size of 260 being enrolled from 5 Asian countries. Interim safety assessment to evaluate feasibility of this regimen has been planned after approximately every 50 patients enrolled. Results: At data cut-off, 107 patients were included in the combined safety analysis of both treatment arms. Rash (25 patients), neutropenia (37 patients), and diarrhea (37 patients) were reported, with 2 (8%), 33 (89%) and 6 (16%) patients, respectively, having grade 3 or greater events. No unexpected adverse events have been observed with this drug combination. Conclusions: Interim safety analysis of TYTAN study showed no significant safety issues and the Independent Data Monitoring Committee has recommended that the trial proceed as planned. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline Bristol-Myers Squibb, Chugai Pharma, Daiichi Sankyo, EMD Serono, GlaxoSmithKline, sanofi-aventis, Taiho Pharmaceutical, Yakult Honsha GlaxoSmithKline GlaxoSmithKline