Experts Discuss Tislelizumab’s FDA Approval in Esophageal Cancer

The FDA approved the combination of tislelizumab-jsgr (Tevimbra) and platinum-containing chemotherapy as a frontline treatment for adult patients with unresectable or metastatic esophageal squamous cell carcinoma (ESCC) with a tumor PD-L1 expression of 1 or higher on March 4, 2025.This approval was supported by data from the phase 3 RATIONALE-306 trial (NCT03783442).¹

In an interview with Targeted Oncology^TM, Ken Kato, MD, PhD, chief of the department of head and neck, and esophageal medical oncology and gastrointestinal medical oncology at the National Cancer Center Hospital in Tokyo, Japan, and 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, delved into this FDA approval and what it means for oncologists across the world.

Transcription:

0:10 | The FDA approval is for tislelizumab, which is an anti-PD1 antibody, and it is the first FDA approval for this agent in this indication, which is previously untreated patients with advanced squamous cell cancer of tislelizumab in combination with cytotoxic chemotherapy. So, it gives another optionfor patients in various parts of the world.

0:37 | Tislelizumab is an anti-PD-1 antibody made in China. The trial evaluated tislelizumab in combination with platinum-containing chemotherapy regimens. The RATIONALE-306 trial aimed to validatethe additive effect of tislelizumab to baseline chemotherapy and its role in the first-line treatment of esophageal squamous cell carcinoma.

1:08 | RATIONALE-306 was a global phase 3 trial, and it tested whether adding tislelizumab to standard chemotherapy could improve overall survival. And it was a placebo-controlled study, and the trial met its primary end point, which is overall survival. And the median survival was approximately 17 months with tislelizumab and about 10 months in placebo.

1:32 | [The primary result of RATIONALE-306 showed a hazard ratio of 0.66] for the entire population, regardless of PD-L1 positivity. The median survival time for the chemotherapy plus tislelizumab arm was 17.2 months, compared with 10.6 months for chemotherapy alone. For the population with a PD-L1 CPS of 10% or more, the hazard ratio improved to 0.62. Even in the population with a PD-L1 CPS of less than 10%, the hazard ratio was 0.77, which is still favorable compared to the chemotherapy-alone arm. This led to the FDA approval of tislelizumab in combination with platinum-based chemotherapy for the first-line treatment of ESCC.

2:52 | And one of the things that was notable about the results was that 3years later, about 15% of patients in the tislelizumab arm remained free of progression. So, as a durable response, and it is a really remarkable outcome in patients with advanced esophageal squamous cancer.

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