In a Chinese phase II trial reported in the Journal of Clinical Oncology, Li et al found that the first-line combination of disitamab vedotin, tislelizumab, and S-1 was associated with high activity in patients with HER2-overexpressing advance gastric/gastroesophageal junction (GEJ) adenocarcinoma.
Study Details
In the multicenter trial, 57 patients enrolled between February 2023 and July 2024 received disitamab vedotin at 2.5 mg/kg once on day 1, tislelizumab at 200 mg once on day 1, and S-1 at 40 to 60 mg twice daily on days 1 to 14 in 21-day cycles. PD-L1 combined positive score (CPS) was < 1 in 54% of patients. The primary outcome measure was confirmed objective response on independent review.
Key Findings
Confirmed objective response was observed in 51 patients (89.5%, 95% confidence interval [CI] = 78.5%–96.0%), including complete response in 5 (8.8%).
At a median follow-up of 28.2 months, median duration of response was 13.3 months (95% CI = 9.6 months to not reached). Median progression-free survival was 13.8 months (95% CI = 10.3–24.0 months), and median overall survival was 31.9 months (95% CI = 22.1 months to not reached).
Patients with CPS ≥ 1 had an objective response rate of 92.3%, median progression-free survival of 16.7 months, and median overall survival of 31.9 months. Patients with CPS < 1 had an objective response rate of 87.1%, median progression-free survival of 10.0 months, and median overall survival of 25.4 months.
Grade ≥ 3 treatment-related adverse events occurred in 64.9% of patients, most commonly decreased neutrophil count (29.8%), decreased white blood cell count (12.3%), anemia (10.5%), and peripheral motor neuropathy (10.5%). Treatment-related serious adverse events occurred in 19.3% of patients, and discontinuation of all treatment due to treatment-related adverse events occurred in 10.5%.
The investigators concluded: “First-line disitamab vedotin with tislelizumab and S-1 demonstrated remarkable antitumor activity and a manageable safety profile in HER2-overexpressing advanced [gastric/gastroesophageal junction] adenocarcinoma, warranting validation in randomized controlled trials.”
Lian Liu, MD, PhD, of the Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China, is the corresponding author for the Journal of Clinical Oncology article.
DISCLOSURE: The study was supported by the National Natural Science Foundation of China and the Young Elite Sponsorship Program of Shandong Provincial Medical Association. For full disclosures of the study authors, visit ascopubs.org.
