Tislelizumab Gains FDA Nod in Advanced Esophageal Cancer

Harry H. Yoon, MD, MHS, discusses the recent FDA approval of tislelizumab and platinum-containing chemotherapy for the frontline treatment of unresectable or metastatic esophageal squamous cell carcinoma whose tumors express PD-L1 at a level of 1 or higher.

Harry H. Yoon, MD, MHS, professor of oncology, enterprise co-leader, gastrointestinal and hepatobiliary/pancreatic cancer research program, enterprise vice-chair, gastrointestinal cancer disease group, associate chair for translational research, department of oncology at the Mayo Clinic Comprehensive Cancer Center, discusses the recent FDA approval of tislelizumab-jsgr (Tevimbra) in combination with platinum-containing chemotherapy for the frontline treatment of adult patients with unresectable or metastatic esophageal squamous cell carcinoma (ESCC) whose tumors express PD-L1 at a level of 1 or higher.

This approval is supported by findings from the phase 3 RATIONALE-306 trial (NCT03783442), which demonstrated a significant improvement in overall survival (OS) for patients receiving the tislelizumab combination compared with chemotherapy alone.

In the RATIONALE-306 trial, a global, double-blind, parallel-arm study conducted across 162 centers in Asia, Europe, North America, and Oceana, patients were randomized 1:1 to receive either tislelizumab plus chemotherapy or placebo plus chemotherapy. The tislelizumab group (n = 326) showed a median OS of 17.2 months (95% CI, 15.8-20.1), compared with 10.6 months (95% CI, 9.3-12.1) in the placebo group (n = 323), with a stratified hazard ratio (HR) of 0.66 (95% CI, 0.54-0.80; 1-sided P < .0001). This represents a 34% reduction in the risk of death, highlighting the clinical benefit of the tislelizumab combination.

Patients received tislelizumab 200 mg or placebo intravenously every 3 weeks, alongside an investigator-chosen chemotherapy regimen. Eligible patients were aged 18 or older with unresectable, locally advanced, recurrent, or metastatic ESCC, regardless of PD-L1 expression, and had measurable or evaluable disease per RECIST 1.1 criteria. The study’s primary endpoint was OS, with secondary endpoints including progression-free survival, objective response rate, and safety.

The trial’s results underscore the potential of tislelizumab as a transformative treatment option for patients with advanced ESCC, particularly those with PD-L1 expression. This approval marks a significant advancement in addressing the unmet needs of this patient population.

REFERENCES

1. Tevimbra approved in US for first-line treatment of advanced esophageal squamous cell carcinoma in combination with chemotherapy. News release. BeiGene, Ltd. March 4, 2025. Accessed March 11, 2025. https://tinyurl.com/bdzy9e59

2. Xu J, Kato K, Raymond E, et al. Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first-line treatment for advanced or metastatic oesophageal squamous cell carcinoma (RATIONALE-306): a global, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2023;24(5):483-495. doi:10.1016/S1470-2045(23)00108-0