Efficacy of Tislelizumab Plus Chemotherapy in Treating ESCC

A recent subgroup analysis from the RATIONALE-306 study has provided compelling evidence supporting the efficacy of combining tislelizumab with chemotherapy as a first-line treatment for patients with locally advanced esophageal squamous cell carcinoma (ESCC). This analysis was presented at the 2025 ESMO Gastrointestinal Cancers Congress, held from July 2-5 in Barcelona, Spain.

The study focused on a specific subgroup of patients with locally advanced ESCC, explaining that tislelizumab, an immune checkpoint inhibitor, when used in combination with standard chemotherapy, significantly improved overall survival (OS) and progression-free survival (PFS) compared to chemotherapy alone. According to Dr. Eric Van Cutsem, MD, PhD, of the Division of Digestive Oncology at University Hospitals Gasthuisberg and KU Leuven, the results were noteworthy, particularly in patients exhibiting a PD-L1 tumor area positivity (TAP) score of 5% or higher.

In the analyzed subgroup of 49 patients treated with tislelizumab plus chemotherapy, the median OS was reported at 25.6 months (95% CI, 19.4-36.3), which starkly contrasts with the 12.3 months (95% CI, 9.0-21.7) observed in the 39 patients receiving chemotherapy alone, indicating a 51% reduction in the risk of death (HR, 0.49; P = .0037). Furthermore, the 12- and 24-month OS rates for the tislelizumab group were 78.5% and 53.5%, respectively, compared to 50.9% and 22.6% for the placebo group.

The median PFS for the tislelizumab cohort was 9.7 months (95% CI, 6.9-19.6), compared to 6.9 months (95% CI, 4.2-9.7) for those on chemotherapy alone (HR, 0.56; P = .0262). In patients with a PD-L1 TAP score of 5% or higher, the median OS increased to 26.4 months (95% CI, 15.3-NE) for those receiving the combination therapy, a remarkable 63% risk reduction in death compared to 11.5 months (95% CI, 8.6-19.8) for the chemotherapy-only group (HR, 0.37; P = .0067).

The safety profile of tislelizumab was consistent with previous studies, with no new safety signals reported. Adverse events were observed in nearly all patients, but the incidence of severe adverse effects was comparable between the treatment and placebo groups. Notably, 100% of patients in the tislelizumab group experienced at least one treatment-emergent adverse event (TEAE).

The RATIONALE-306 study is a double-blind, randomized, global phase 3 clinical trial that enrolled patients with unresectable local advanced or metastatic ESCC who had not received prior systemic therapy for advanced disease. Participants were randomized to receive either 200 mg of tislelizumab every three weeks plus chemotherapy or placebo with chemotherapy.

The implications of these findings are significant. The FDA approved tislelizumab in March 2025 for first-line use in adult patients with unresectable or metastatic ESCC exhibiting a PD-L1 expression of 1% or higher based on data from this study. This marks a pivotal advancement in treatment options for this challenging disease.

Further research is warranted to explore the long-term benefits and potential applications of tislelizumab in other cancer subtypes. Overall, the RATIONALE-306 subgroup analysis highlights the promise of immunotherapy in improving outcomes for patients battling locally advanced ESCC, providing a new avenue for effective treatment in a patient population with limited options.