# Real-World Efficacy and Safety of Disitamab Vedotin (RC48-ADC) in the Treatment of HER2-Overexpressing Advanced Gastric/Gastroesophageal Junction Cancer

## TL;DR

Disitamab vedotin shows promise in treating advanced stomach cancer that overproduces HER2, with tumor shrinkage in a third of patients and manageable side effects.

## Contribution

This study provides real-world evidence of disitamab vedotin's efficacy and safety in HER2-overexpressing gastric cancer after prior treatments failed.

## Key findings

- About one-third of patients experienced tumor shrinkage, and two-thirds had disease control.
- Median progression-free survival was 6.5 months and overall survival was 13.5 months.
- Anemia was the most common side effect, but the drug was generally well tolerated.

## Abstract

In this real-world study of patients with advanced stomach or gastroesophageal cancer that overproduces a protein called HER2, researchers tested a new targeted drug called disitamab vedotin after other treatments had failed. About one-third of these patients saw their tumors shrink and nearly two-thirds had their disease controlled. On average, patients lived for about 6.5 months before their cancer worsened and about 13.5 months overall after starting the treatment. The most common side effect was anemia, but the drug was generally well tolerated. These findings suggest that disitamab vedotin could be a promising new option for patients whose cancer continued progressing despite previous therapies, and they support further research and updates to treatment guidelines.

Objective: To evaluate the real-world efficacy and safety of disitamab vedotin (RC48-ADC) in patients with human epidermal growth factor receptor 2 (HER2) overexpression (immunohistochemistry [IHC] 2+ or 3+), advanced gastric/gastroesophageal junction cancer (GC/GEJC) with metastases who had received at least one line of prior systemic therapy. Patients and methods: Patients with HER2-overexpressing advanced or metastatic GC/GEJC who had previously received the anti-HER2 antibody-drug conjugate disitamab vedotin between December 2022 and April 2024 were enrolled in this study. The patients’ baseline characteristics, treatment procedures, and laboratory or imaging examinations were retrospectively collected and analyzed. The observation items included the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs). Results: Of the 38 enrolled patients in the study, 27 were found to be HER2-positive. Most patients (29/38) received disitamab vedotin therapy as a third-line or subsequent treatment. A total of 68.4% of patients had previously received anti-HER2 therapy, and 13 patients underwent immunotherapy concurrently. The overall ORR and DCR were 31.6% and 65.8%, respectively. A higher ORR was observed in patients with a single metastatic site compared to those with multiple sites (53.3% vs. 17.4%, p = 0.022). In the general population, the median PFS was 6.5 months (95% confidence interval [CI] 3.3–9.8 months), and OS was 13.5 months (95% CI 9.0–17.9 months). The most common adverse event was anemia (89.5%), and eight patients suffered severe toxicities of grade ≥3. Conclusions: Disitamab vedotin exhibited encouraging anti-tumor effectiveness with a tolerable safety profile for advanced GC/GEJC patients with HER2 overexpression who had failed at least one line of systemic therapy in a real-world setting.