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)

E Van Cutsem,H Chung,Y Bang,Y Bang,Y Kang,Y Kang,L Shen,L Shen,J Hill,A Feyereislova,H Chung,Y Kang,A Feyereislova,L Shen,Y Kang,J Hill,A Sawaki,F Lordick,M Lehle,L Shen,J Hill,M Lehle,A Feyereislova,H Chung,M Lehle,A Sawaki,H Chung,A Feyereislova,Y Bang,A Sawaki,F Lordick,L Shen,M Lehle,Y Kang,A Feyereislova,A Sawaki,A Sawaki,Y Bang,F Lordick,Y Bang,H Chung,J Hill,A Sawaki,F Lordick,F Lordick,M Lehle,J Hill,Y Kang,L Shen,M Lehle,F Lordick,H Chung,J Hill,Y Bang,A Feyereislova

doi:10.1200/jco.2009.27.18s.lba4509

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. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Hoffman-La Roche, Roche Products Pty Ltd Roche Hoffman-La Roche, Roche Hoffman-La Roche, Roche Hoffman-La Roche, Roche

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