TY - JOUR
T1 - Tislelizumab Versus Chemotherapy as Second-Line Treatment for Advanced or Metastatic Esophageal Squamous Cell Carcinoma (RATIONALE-302)
T2 - A Randomized Phase III Study
AU - Shen, Lin
AU - Kato, Ken
AU - Kim, Sung Bae
AU - Ajani, Jaffer A.
AU - Zhao, Kuaile
AU - He, Zhiyong
AU - Yu, Xinmin
AU - Shu, Yongqian
AU - Luo, Qi
AU - Wang, Jufeng
AU - Chen, Zhendong
AU - Niu, Zuoxing
AU - Zhang, Longzhen
AU - Yi, Tienan
AU - Sun, Jong Mu
AU - Chen, Jianhua
AU - Yu, Guohua
AU - Lin, Chen Yuan
AU - Hara, Hiroki
AU - Bi, Qing
AU - Satoh, Taroh
AU - Pazo-Cid, Roberto
AU - Arkenau, Hendrick Tobias
AU - Borg, Christophe
AU - Lordick, Florian
AU - Li, Liyun
AU - Ding, Ningning
AU - Tao, Aiyang
AU - Shi, Jingwen
AU - Van Cutsem, Eric
N1 - Publisher Copyright:
© American Society of Clinical Oncology.
PY - 2022/4/1
Y1 - 2022/4/1
N2 - PURPOSEPatients with advanced or metastatic esophageal squamous cell carcinoma (ESCC) have poor prognosis. For these patients, treatment options are limited after first-line systemic therapy.PATIENTS AND METHODSIn this open-label phase III clinical study, patients with advanced or metastatic ESCC, whose tumor progressed after first-line systemic treatment, were randomly assigned (1:1) to receive intravenous tislelizumab, an anti-programmed cell death protein 1 antibody, 200 mg every 3 weeks or chemotherapy (investigator's choice of paclitaxel, docetaxel, or irinotecan). The primary end point was overall survival (OS) in all patients. The key secondary end point was OS in patients with programmed death-ligand 1 tumor area positivity (TAP) score ≥ 10%.RESULTSIn total, 512 patients across 11 countries/regions were randomly assigned. At final analysis, conducted after 410 death events occurred, OS was significantly longer with tislelizumab versus chemotherapy in all patients (median, 8.6 v 6.3 months; hazard ratio [HR], 0.70 [95% CI, 0.57 to 0.85]; one-sided P =.0001), and in patients with TAP ≥ 10% (median, 10.3 months v 6.8 months; HR, 0.54 [95% CI, 0.36 to 0.79]; one-sided P =.0006). Survival benefit was consistently observed across all predefined subgroups, including those defined by baseline TAP score, region, and race. Treatment with tislelizumab was associated with higher objective response rate (20.3% v 9.8%) and a more durable antitumor response (median, 7.1 months v 4.0 months) versus chemotherapy in all patients. Fewer patients experienced ≥ grade 3 treatment-related adverse events (18.8% v 55.8%) with tislelizumab versus chemotherapy.CONCLUSIONTislelizumab significantly improved OS compared with chemotherapy as second-line therapy in patients with advanced or metastatic ESCC, with a tolerable safety profile. Patients with programmed death-ligand 1 TAP ≥ 10% also demonstrated statistically significant survival benefit with tislelizumab versus chemotherapy.
AB - PURPOSEPatients with advanced or metastatic esophageal squamous cell carcinoma (ESCC) have poor prognosis. For these patients, treatment options are limited after first-line systemic therapy.PATIENTS AND METHODSIn this open-label phase III clinical study, patients with advanced or metastatic ESCC, whose tumor progressed after first-line systemic treatment, were randomly assigned (1:1) to receive intravenous tislelizumab, an anti-programmed cell death protein 1 antibody, 200 mg every 3 weeks or chemotherapy (investigator's choice of paclitaxel, docetaxel, or irinotecan). The primary end point was overall survival (OS) in all patients. The key secondary end point was OS in patients with programmed death-ligand 1 tumor area positivity (TAP) score ≥ 10%.RESULTSIn total, 512 patients across 11 countries/regions were randomly assigned. At final analysis, conducted after 410 death events occurred, OS was significantly longer with tislelizumab versus chemotherapy in all patients (median, 8.6 v 6.3 months; hazard ratio [HR], 0.70 [95% CI, 0.57 to 0.85]; one-sided P =.0001), and in patients with TAP ≥ 10% (median, 10.3 months v 6.8 months; HR, 0.54 [95% CI, 0.36 to 0.79]; one-sided P =.0006). Survival benefit was consistently observed across all predefined subgroups, including those defined by baseline TAP score, region, and race. Treatment with tislelizumab was associated with higher objective response rate (20.3% v 9.8%) and a more durable antitumor response (median, 7.1 months v 4.0 months) versus chemotherapy in all patients. Fewer patients experienced ≥ grade 3 treatment-related adverse events (18.8% v 55.8%) with tislelizumab versus chemotherapy.CONCLUSIONTislelizumab significantly improved OS compared with chemotherapy as second-line therapy in patients with advanced or metastatic ESCC, with a tolerable safety profile. Patients with programmed death-ligand 1 TAP ≥ 10% also demonstrated statistically significant survival benefit with tislelizumab versus chemotherapy.
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U2 - 10.1200/JCO.21.01926
DO - 10.1200/JCO.21.01926
M3 - Article
C2 - 35442766
AN - SCOPUS:85130203678
SN - 0732-183X
VL - 71
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
M1 - JCO.21.01926
ER -