In the phase III RATIONALE-302 trial reported in the Journal of Clinical Oncology, Shen et al found that the anti–PD-1 antibody tislelizumab significantly improved overall survival vs chemotherapy in the second-line treatment of patients with advanced or metastatic esophageal squamous cell carcinoma.
In the open-label trial, 512 patients (95% with metastatic disease) from sites in Asia (n = 404, 78.9%) and Europe and North America (n = 108, 21.1%) were randomly assigned between January 2018 and March 2020 to receive tislelizumab at 200 mg every 3 weeks (n = 256) or investigator’s choice of chemotherapy with paclitaxel, docetaxel, or irinotecan (n = 256). Paclitaxel (n = 85) was given at 135 to 175 mg/m2 once every 3 weeks or at 80 to 100 mg/m2 once weekly per regional guidelines; in Japan, paclitaxel was given at 100 mg/m2 in cycles consisting of once weekly dosing for 6 weeks followed by 1 week of rest. Docetaxel (n = 53) was given at 75 mg/m2 once every 3 weeks (70 mg/m2 once every 3 weeks in Japan). Irinotecan (n = 118) was given at 125 mg/m2 on days 1 and 8 every 21 days.
The primary endpoint was overall survival in all patients. The key secondary endpoint was overall survival among patients with PD-L1 tumor area positivity score ≥ 10%.
Overall Survival
At final analysis (after 410 deaths), median follow-up was 8.5 months (range = 0.2–31.7 months) in the tislelizumab group and 5.8 months (range = 0.0–30.8 months) in the chemotherapy group.
Among all patients, median overall survival was 8.6 months (95% confidence interval [CI] = 7.5–10.4 months) in the tislelizumab group vs 6.3 months (95% CI = 5.3–7.0 months) in the chemotherapy group (hazard ratio [HR] = 0.70, 95% CI = 0.57–0.85, P = .0001). Rates at 12 months were 37.4% vs 23.7%.
A total of 157 patients (30.7%) had PD-L1 tumor area positivity ≥ 10% tumors, including more patients in the tislelizumab group (34.8% v 26.6%). Among these patients, median overall survival was 10.3 months (95% CI = 8.5–16.1 months) in the tislelizumab group vs 6.8 months (95% CI = 4.1–8.3 months) in the chemotherapy group (HR = 0.54, 95% CI = 0.36–0.79, P = .0006). Among 218 patients with tumor area positivity < 10% tumors, median overall survival was 6.9 months vs 5.8 months (HR = 0.82, 95% CI = 0.62–1.09). Among 99 patients without known tumor area positivity status, median overall survival was 9.8 vs 7.0 months (HR = 0.67, 95% CI = 0.41–1.12).
Among all patients, objective response was observed in 20.3% of the tislelizumab group vs 9.8% of the chemotherapy group, with median response durations of 7.1 months vs 4.0 months. Among all patients, median progression-fee survival was 1.6 vs 2.1 months (HR = 0.83, 95% CI = 0.67–1.01), with rates at 6 and 12 months of 21.7% vs 14.9% and 12.7% vs 1.9%.
KEY POINTS
- Tislelizumab significantly prolonged overall survival vs chemotherapy among all patients.
- Survival benefit was observed in the subgroup of patients with PD-L1 tumor area positivity ≥ 10% tumors.
Adverse Events
The most common treatment-related adverse events of any grade were increased aspartate aminotransferase (11.4%), anemia (11.0%), and hypothyroidism (10.2%) in the tislelizumab group, and decreased white blood cell count (40.8%), decreased neutrophil count (39.2%), and anemia (34.6%) in the chemotherapy group. Grade ≥ 3 treatment-related adverse events occurred in 18.8% of patients in the tislelizumab group vs 55.8% of the chemotherapy group. Serious treatment-related adverse events occurred in 14.1% vs 19.6% of patients. Treatment-related adverse events led to death in seven patients (2.7%) vs eight patients (3.3%).
The investigators concluded, “Tislelizumab significantly improved overall survival compared with chemotherapy as second-line therapy in patients with advanced or metastatic esophageal squamous cell carcinoma, with a tolerable safety profile. Patients with PD-L1 [tumor area positivity] ≥ 10% also demonstrated a statistically significant survival benefit with tislelizumab vs chemotherapy.”
Lin Shen, MD, PhD, of the Department of Gastrointestinal Oncology, Beijing Cancer Hospital, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by BeiGene, Ltd. For full disclosures of the study authors, visit ascopubs.org.
