Trastuzumab Deruxtecan or Ramucirumab plus Paclitaxel in Gastric Cancer
Clinical knowledge base written and curated by GastroAGI Team from primary medical literatureLast updated August 1, 2025
The international, randomized phase 3 clinical trial compared trastuzumab deruxtecan with ramucirumab plus paclitaxel as second-line treatment options for patients with HER2-positive metastatic gastric or gastroesophageal junction adenocarcinoma who had previously progressed on trastuzumab-based therapy. Below are the key findings and details from the study:
Efficacy Outcomes
- Overall Survival (OS):
- Trastuzumab deruxtecan demonstrated significantly longer overall survival compared to ramucirumab plus paclitaxel:
- 14.7 months vs. 11.4 months.
- Hazard Ratio (HR): 0.70, indicating a 30% reduction in the risk of death with trastuzumab deruxtecan.
- Progression-Free Survival (PFS):
- Trastuzumab deruxtecan also showed improvements in progression-free survival, though specific numbers were not provided in the context.
- Objective Response Rate (ORR):
- Trastuzumab deruxtecan achieved a higher objective response rate compared to ramucirumab plus paclitaxel:
- 44.3% vs. 29.1%.
Safety and Adverse Events
- Adverse Events:
- Both treatment groups experienced common adverse events, with high-grade toxicities occurring in approximately 50% of patients.
- Drug-Related Interstitial Lung Disease (ILD) or Pneumonitis:
- Trastuzumab deruxtecan carried a higher risk of drug-related interstitial lung disease or pneumonitis, occurring in 13.9% of patients.
- Most cases were low grade, but this is a notable safety concern.
Conclusion
- Trastuzumab deruxtecan demonstrated superior survival benefits and greater efficacy compared to ramucirumab plus paclitaxel in the second-line setting for HER2-positive gastric cancer.
- Despite the increased risk of interstitial lung disease or pneumonitis, trastuzumab deruxtecan has been confirmed as an effective second-line therapeutic option for this patient population.
This study highlights trastuzumab deruxtecan as a promising treatment choice, offering significant improvements in survival and response rates for patients with HER2-positive metastatic gastric cancer.
