PET/CT-Guided Neoadjuvant Tislelizumab plus Chemotherapy/Chemoradiotherapy for Resectable Esophageal Squamous Cell Carcinoma: RATIONALE-213 Final Analysis

Clinical Snapshot

Key Findings

• P Value: Not reported in abstract

• Effect Size: pCR rates comparable between cohorts despite different treatment intensities

• Primary Outcome: pCR rate: 30% (95% CI 11.9-54.3) in PET responders; 34.4% (95% CI 18.6-53.2) in PET nonresponders

• Nnt Or Sensitivity: Approximately 3-4 patients needed to treat for one pCR based on observed rates

• Confidence Interval: Wide CIs reflecting small sample size: 11.9-54.3% and 18.6-53.2%

Clinical Application

Requires PET/CT imaging capability and access to tislelizumab; complex multimodal treatment coordination needed Tislelizumab not currently PBS-listed; would require special access scheme. PET/CT widely available. Approach aligns with emerging personalised cancer care frameworks Patients with resectable ESCC suitable for neoadjuvant therapy, particularly those with adequate performance status

Abstract

PURPOSE: The aim of this study is to assess positron emission tomography/computed tomography (PET/CT)-guided neoadjuvant treatment with tislelizumab plus chemotherapy/chemoradiotherapy in patients with resectable esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: RATIONALE-213, a multicenter, open-label, two-cohort phase II study, enrolled 70 patients with resectable ESCC. After one induction chemotherapy cycle, patients were categorized as PET responders (PET maximum standardized uptake value decrease ≥35%) or PET nonresponders (<35%). Subsequently, all patients received three cycles of tislelizumab 200 mg intravenously. In addition, PET responders received chemotherapy and PET nonresponders received chemoradiotherapy as neoadjuvant treatment followed by surgery. The primary endpoint was the pathologic complete response (pCR) rate. RESULTS: As of October 25, 2024 (median follow-up 25.5 months), pCR rates were 30% [95% confidence interval (CI), 11.9-54.3] in PET responders and 34.4% (95% CI, 18.6-53.2) in PET nonresponders. Higher pCR rates were associated with higher baseline programmed cell death ligand 1 tumor area positivity scores in both cohorts. One-year disease-free survival rates were 79% and 74.2%, and event-free survival rates were 87.1% and 67.8%, respectively. Any-grade and grade ≥3 treatment-related adverse events (TRAE) occurred in 93.3% and 50% of PET responders and 97.5% and 82.5% of PET nonresponders, with no new safety signals. The most common grade ≥3 TRAE was decreased neutrophil count (36.7% and 70%, respectively). CONCLUSIONS: Tislelizumab with chemotherapy/chemoradiotherapy as neoadjuvant treatment for resectable ESCC yielded promising pCR rates and favorable survival outcomes with a tolerable safety profile in both PET/CT-guided responders and PET nonresponders.

References

1. 1.Yang, Y., Yan, X., Jiang, H., Kang, M., Mei, X., Tan, L., Liu, J., Du, W., Shi, Y., Zhang, Z., Liang, L., Liao, Y., & Chen, L. (2026). PET/CT-Guided Neoadjuvant Tislelizumab plus Chemotherapy/Chemoradiotherapy for Resectable Esophageal Squamous Cell Carcinoma: RATIONALE-213 Final Analysis. Clinical Cancer Research. https://doi.org/10.1158/1078-0432.CCR-25-2367