ToGA (Bang 2010): trastuzumab with chemotherapy for HER2-positive advanced gastric cancer
The trial that brought HER2 testing and trastuzumab to stomach cancer: adding the antibody to chemotherapy prolonged survival in patients whose gastric or junction cancers overexpressed HER2, about a fifth of those screened.
Overview
ToGA screened 3,665 patients with advanced gastric or gastro-oesophageal junction cancer and found HER2 positivity in 22.1%. It randomised 594 HER2-positive patients to trastuzumab plus cisplatin and a fluoropyrimidine or to chemotherapy alone. Trastuzumab improved overall survival, progression-free survival and response rate, with the largest benefit in tumours with high HER2 expression (immunohistochemistry 3+ or 2+ with amplification), which became the definition of HER2 positivity used for gastric cancer.
- HER2 positivity in 22.1% of 3,665 screened patients; 594 randomised to trastuzumab plus chemotherapy or chemotherapy alone.
- Median overall survival 13.8 vs 11.1 months, hazard ratio 0.74.
- In tumours with IHC 3+ or IHC 2+ and FISH-positive HER2: median overall survival 16.0 vs 11.8 months.
- Response rate 47% vs 35%; no increase in cardiac events of note.
ToGA made gastric cancer the second disease treated by HER2 status and introduced gastric-specific HER2 scoring. It is the base on which trastuzumab deruxtecan and pembrolizumab combinations in HER2-positive gastric cancer have built.
- Open-label design.
- Benefit was concentrated in high HER2 expressers; IHC 2+ FISH-negative and IHC 0 or 1+ FISH-positive tumours gained little.
- Chemotherapy backbone was cisplatin with capecitabine or fluorouracil.
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