Dr Bekaii-Saab on the RATIONALE-306 Study of Tislelizumab Plus Chemotherapy in Esophageal Cancer

“When we have a new agent that is approved by the FDA that is similar to the other 2 that are already approved, [the question is,] What patient population should be considered for the new agent vs the agents that are already established? Unfortunately, at this time, we do not have a differentiator.”

Tanios S. Bekaii-Saab, MD, FACP, leader, Gastrointestinal Cancer Program, Mayo Clinic Comprehensive Cancer Center, medical director, Cancer Clinical Research Office, vice chair and section chief for medical oncology, Department of Internal Medicine, Mayo Clinic, discussed the use of tislelizumab-jsgr (Tevimbra) plus chemotherapy for the treatment of patients with unresectable or metastatic esophageal squamous cell carcinoma (ESCC).

In March 2025, the FDA approved tislelizumab in combination with platinum-containing chemotherapy for the frontline treatment of adult patients with unresectable or metastatic ESCC with a PD-L1 expression level of 1 or higher. The approval was supported by data from the phase 3 RATIONALE-306 trial (NCT03783442); at a median follow-up of 16.3 months (IQR, 8.6-21.8), patients who received the combination (n = 326) achieved a median overall survival (OS) of 17.2 months (95% CI, 15.8-20.1). Comparatively, at a median follow-up of 9.8 months (IQR, 5.8-19.0), patients who received placebo plus chemotherapy (n = 323) experienced a median OS of 10.6 months (95% CI, 9.3-12.1).

Additional data from RATIONALE-306 showed that the median progression-free survival (PFS) in the combination and placebo arms was 7.3 months (95% CI, 6.9-8.3) vs 5.6 months (95% CI, 4.9-6.0). The 36-month PFS rates were 15.0% (95% CI, 10.8%-19.9%) and 2.9% (95% CI, 1.1%-6.2%), respectively.

The role of chemoimmunotherapy is well established in patients with PD-L1–positive disease, Bekaii-Saab said. Patients have good outcomes with this approach, especially those with a PD-L1 combined positive score of 5 or higher, he added.

A new challenge following the approval of tislelizumab is determining whether it is superior to fluoropyrimidine- and platinum-based chemotherapy plus nivolumab (Opdivo) or pembrolizumab (Keytruda), which is unknown, Bekaii-Saab explained. Patients who receive any of these agents tend to have fairly similar outcomes, he continued. Specific patient populations with ESCC who are the most well-suited for tislelizumab vs nivolumab or pembrolizumab are still being determined, he concluded.