Tislelizumab Plus Chemotherapy as First-line Treatment for Advanced Esophageal Squamous Cell Carcinoma and Gastric/Gastroesophageal Junction Adenocarcinoma

Purpose:
This phase II study (NCT03469557) evaluated the safety, tolerability, and antitumor activity of first-line tislelizumab—a monoclonal antibody targeting programmed cell death-1 (PD-1)—in combination with chemotherapy in patients with locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) or gastric/gastroesophageal junction (G/GEJ) adenocarcinoma.
Patients and Methods:
Patients with ESCC received tislelizumab (200 mg IV every 3 weeks) alongside cisplatin (80 mg/m² IV Q3W for up to 6 cycles) and fluorouracil (800 mg/m²/day IV on Days 1–5 Q3W for up to 6 cycles). Those with G/GEJ adenocarcinoma were treated with tislelizumab (200 mg IV Q3W), oxaliplatin (130 mg/m² IV Q3W for up to 6 cycles), and oral capecitabine (1,000 mg/m² twice daily on Days 1–14 Q3W). The primary endpoint was safety and tolerability; secondary endpoints included objective response rate (ORR), duration of response (DoR), disease control rate (DCR), and progression-free survival per RECIST v1.1. Exploratory endpoints included overall survival and potential predictive biomarkers.
Results:
As of March 31, 2019, 30 patients (15 per cohort) were enrolled. The most common treatment-related adverse events were anemia (n=18), decreased appetite (n=17), nausea (n=16), and asthenia (n=15). One patient Cytidine experienced fatal hepatic dysfunction—deemed treatment-related by the investigator—though confounded by disease progression and underlying hepatitis. Confirmed ORRs and DCRs were both 46.7% and 80%, respectively, in both cohorts. In ESCC, the median DoR was 12.8 months (95% CI: 3.5–12.8); DoR was not yet mature in the G/GEJ cohort.
Conclusions:
Tislelizumab combined with chemotherapy produced durable responses and showed a manageable safety profile in patients with advanced ESCC or G/GEJ adenocarcinoma.