Trastuzumab Deruxtecan or Ramucirumab plus Paclitaxel in Gastric Cancer

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**

1. **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.

2. **Progression-Free Survival (PFS):**

• Trastuzumab deruxtecan also showed improvements in progression-free survival, though specific numbers were not provided in the context.

3. **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**

1. **Adverse Events:**

• Both treatment groups experienced common adverse events, with high-grade toxicities occurring in approximately **50% of patients**.

2. **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.