- Trastuzumab deruxtecan, an anti-HER2 antibody linked to a cytotoxic topoisomerase I inhibitor, led to improvements in response and OS as third-line therapy in patients with previously treated HER2-positive gastric cancer.
Why this matters
- Existing third-line therapies have limited benefit in this population.
- Open-label, multicenter, phase 2 trial in Japan and South Korea.
- 187 patients were randomly assigned to trastuzumab deruxtecan or clinician's choice of therapy (DESTINY-Gastric01).
- Funding: Daiichi Sankyo.
- Trastuzumab deruxtecan is attached to a cytotoxic topoisomerase I inhibitor by a linker that is cleaved by enzymes overexpressed in tumor cells.
- Compared with the clinician's choice group, the trastuzumab deruxtecan group had:
- Higher objective response rate (51% vs 14%; P<.001>
- Longer median duration of confirmed objective responses (11.3 vs 3.9 months).
- Longer median OS (12.5 vs 8.4 months; HR for death, 0.59; P=.01).
- Longer median PFS (5.6 vs 3.5 months; HR for disease progression or death, 0.47; 95% CI, 0.31-0.71).