Adding tislelizumab to platinum-based chemotherapy improves outcomes in patients with treatment-naïve, advanced esophageal cancer, according to research published in The Lancet Oncology.

Researchers found that overall survival (OS) and progression-free survival (PFS) were longer in patients who received tislelizumab plus chemotherapy than in patients who received chemotherapy alone. 

These results come from the double-blind, phase 3 RATIONALE-306 trial ( Identifier: NCT03783442). The trial enrolled 649 patients with previously untreated, unresectable, advanced esophageal squamous cell carcinoma. 

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The patients were randomly assigned to receive investigator’s choice of chemotherapy in combination with either tislelizumab at 200 mg (n=326) or placebo (n=323) every 3 weeks on day 1. Chemotherapy consisted of a platinum agent (cisplatin or oxaliplatin) plus a fluoropyrimidine (fluorouracil or capecitabine) or paclitaxel.

Baseline characteristics were similar between the treatment arms. The median age was 64 years in the tislelizumab arm and 65 years in the placebo arm. Most patients had metastatic disease (86% and 87%, respectively). In both arms, 87% of patients were men, and 75% were Asian.

The median follow-up was 16.3 months in the tislelizumab arm and 9.8 months in the placebo arm. The primary endpoint was OS.

The median OS was 17.2 months with tislelizumab and 10.6 months with placebo (hazard ratio [HR], 0.66; 95% CI, 0.54-0.80; P <.0001). The benefit with tislelizumab was seen regardless of PD-L1 expression level. 

The 12-month OS rate was 65.0% in the tislelizumab arm and 44.9% in the placebo arm. The 18-month OS rate was 48.6% and 34.5%, respectively.

The median PFS was 7.3 months with tislelizumab and 5.6 months with placebo (HR, 0.62; 95% CI, 0.52-0.75; P <.0001). The 12-month PFS rate was 30.0% with tislelizumab and 15.7% with placebo.

The objective response rate was improved with tislelizumab as well. It was 63% with tislelizumab and 42% with placebo (odds ratio, 2.38; 95% CI, 1.73-3.27; P <.0001).

Grade 3-5 treatment-related adverse events (TRAEs) occurred in 67% of patients in the tislelizumab arm and 64% of patients in the placebo arm. The most common grade 3-4 TRAEs in both arms were decreased neutrophil count, anemia, and decreased white blood cell count. There were 6 patients in the tislelizumab arm and 4 in the placebo arm who died of TRAEs. 

“First-line treatment of advanced or metastatic esophageal squamous cell carcinoma with tislelizumab plus chemotherapy resulted in significant and clinically meaningful overall survival benefit versus placebo plus chemotherapy,” the researchers concluded. “The safety profile of tislelizumab in combination with chemotherapy was manageable, with no new safety signals identified.”

Disclosures: This research was supported by BeiGene. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures. 


Xu J, Kato K, Raymond E, 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. Published online April 17, 2023. doi:10.1016/S1470-2045(23)00108-0