First-line tislelizumab plus chemotherapy prolongs survival in metastatic or advanced ESCC

May 2023 Cancer trials Andrea Enguita
Esophageal cancer, 3D illustration showing malignant tumor in the human esophagus

Previously, second-line tislelizumab demonstrated to improve survival of patients with metastatic or advanced oesophageal squamous cell carcinoma (ESCC). More recently, the RATIONALE-306 trial has explored the potential of tislelizumab in combination with chemotherapy as a first-line treatment option. The interim analysis results of this trial, published in The Lancet Oncology, shows that first-line tislelizumab plus chemotherapy prolongs survival in patients with advanced or metastatic ESCC, together with a manageable safety profile.

In 2020, oesophageal cancer (EC) was ranked as the seventh most common cancer worldwide and the sixth most common cause of cancer-related deaths. Oesophageal squamous cell carcinoma (ESCC) is the most common histologic subtype, accounting for more than 85% of ECs worldwide. First-line systemic therapy for advanced or metastatic ESCC typically consists of a fluoropyrimidine- and platinum-based regimen. Unfortunately, the outcomes of these patients remain poor. Previously, the RATIONALE-302 trial showed that the anti-PD-1 antibody tislelizumab improves overall survival (OS) in second-line treatment of patients with advanced or metastatic ESCC, compared to chemotherapy.1 The RATIONALE-306 aimed to assess the efficacy and safety of tislelizumab plus chemotherapy as a first-line treatment option for these patients. Here, the interim analysis of the RATIONALE-306 is reported.2


The global phase 3 RATIONALE-306 trial was conducted at 162 medical centres across Asia, Europe, Oceania, and North America. Eligible patients were adults (aged ≥18 years) with unresectable, locally advanced, recurrent or metastatic ESCC. In total, 649 patients were randomly assigned (1:1) to receive tislelizumab (n=326) or placebo (n=323), both in combination with an investigator-chosen chemotherapy doublet, comprising a platinum agent (cisplatin or oxaliplatin) plus a fluoropyrimidine (fluorouracil or capecitabine) or paclitaxel. Treatment was continued until disease progression or unacceptable toxicity. The primary endpoint was overall survival (OS).2

Study findings

After a median follow-up of 16.3 months in the tislelizumab group and 9.8 months in the placebo group, a significant OS benefit was observed with tislelizumab over placebo (17.2 vs. 10.6 months, respectively; HR[95%CI]: 0.66 [0.54-0.80], p<0.0001). As of data cutoff, 60% and 70% of patients in the tislelizumab and placebo group had died, respectively. The most common grade 3 or 4 treatment-related treatment-emergent adverse events were decreased neutrophil count (31% vs. 33% in the tislelizumab and placebo groups, respectively), decreased white blood cell count (11% vs. 16%), and anaemia (15% vs. 13%). Six deaths in the tislelizumab group were determined to be treatment-related, including gastrointestinal and upper gastrointestinal haemorrhages (n=2), myocarditis, pulmonary tuberculosis, electrolyte imbalance, and respiratory failure (n=1 each). In the placebo group, four deaths were considered to be treatment-related, including pneumonia (n=1), septic shock (n=1), and unspecified death n=2).2

This study showed that tislelizumab plus chemotherapy as a first-line treatment for advanced or metastatic ESS provides superior OS compared to placebo plus chemotherapy, together with a manageable safety profile.2


  1. Shen L, Kato K, Kim S-B, et al. Tislelizumab Versus Chemotherapy as Second-Line Treatment for Advanced or Metastatic Esophageal Squamous Cell Carcinoma (RATIONALE-302): A Randomized Phase III Study. J Clin Oncol. 2022;40(26):3065-3076.
  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 May;24(5):483-95.