Efficacy results from the ToGA trial: A phase III study of trastuzumab added to standard chemotherapy (CT) in first-line human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (GC)

Abstract

LBA4509 Background: Advanced GC is an incurable disease; new and less toxic treatments are needed. HER2 overexpression has been reported in 6–35% of stomach and gastroesophageal tumors. Trastuzumab (H; Herceptin), a monoclonal antibody against HER2, has shown survival benefits when given with CT in patients (pts) with HER2-positive early and metastatic breast cancer. The ToGA study is the first randomized, prospective, multicenter, phase III trial to study the efficacy and safety of H in HER2- positive GC. Methods: Pts with HER2-positive gastroesophageal and gastric adenocarcinoma (locally advanced, recurrent, or metastatic) were randomized to receive H+CT (5-fluorouracil or capecitabine and cisplatin) q3w for 6 cycles or CT alone. H was given until disease progression. The primary end point was overall survival (OS); secondary end points included overall response rate (ORR), progression-free survival, time to progression, duration of response, and safety. An interim analysis was planned at 75% of deaths and the Independent Data Monitoring Committee recommended releasing the data as the pre-specified boundary was exceeded and median follow-up of pts was 17.1 months. Results: Tumors from 3,807 pts were centrally tested for HER2 status: 22.1% were HER2 positive (abstract #4556). 594 pts were randomized 1:1 at sites in Europe, Latin America, and Asia. Baseline characteristics were well balanced across arms. Median OS was significantly improved with H+CT compared to CT alone: 13.5 vs. 11.1 months, respectively (p=0.0048; HR 0.74; 95% CI 0.60, 0.91). ORR was 47.3% in the H+CT arm and 34.5% in the CT arm (p=0.0017). Safety profiles were similar with no unexpected adverse events in the H+CT arm. There was no difference in symptomatic congestive heart failure between arms. Asymptomatic left ventricular ejection fraction decreases were reported in 4.6% of pts in the H+CT arm and 1.1% in the CT arm. Conclusions: This first randomized trial investigating anti-HER2 therapy in advanced GC showed that H+CT is superior to CT alone. The OS benefit indicates that H is a new, effective, and well-tolerated treatment for HER2-positive GC. [Table: see text]