Jianming Xu, Ken Kato, Richard Hubner, Sook Ryun Park, Takashi Kojima, Ryu Ishihara, Lucjan Wyrwicz, Eric Van Cutsem, Paula Jimenez-Fonseca, Hongqian Wu, Lei Wang, Sebastian Yan, Jingwen Shi, Alysha Kadva, Harry H. Yoon
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Therefore, we conducted a retrospective analysis of RATIONALE-306 to evaluate the efficacy and safety of tislelizumab plus investigator-chosen chemotherapy (ICC) versus placebo plus ICC in patients with advanced or metastatic unresectable ESCC and a PD-L1 TAP score ≥ 1%.</p><h3>Methods</h3><p>Adult patients with advanced or metastatic unresectable ESCC enrolled in the global, randomized, phase 3 RATIONALE-306 trial randomly received tislelizumab 200 mg every 3 weeks plus ICC or matched placebo plus ICC. Efficacy and safety outcomes were evaluated among patients who were retrospectively assessed for PD-L1 expression defined by a TAP score ≥ 1%.</p><h3>Results</h3><p>At primary analysis data cutoff (February 28, 2022), a clinically meaningful improvement in median overall survival was observed among 230 patients in the tislelizumab plus ICC arm {16.8 [95% confidence interval (CI) 15.3–20.8] months} versus 248 patients in the placebo plus ICC arm [9.6 (95% CI 8.9–11.8) months] [stratified hazard ratio 0.64 (95% CI 0.51–0.80)]; this was maintained at a 3-year follow-up data cutoff (November 24, 2023). Similar findings at primary analysis were observed for progression-free survival, objective response rate, disease control rate, and duration of response. 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引用次数: 0
摘要
美国食品和药物管理局肿瘤药物咨询委员会（2024年9月）投票反对将程序性细胞死亡蛋白-1抑制剂用于具有程序性死亡配体1 （PD-L1）表达肿瘤区域阳性（TAP）评分的晚期或转移性不可切除食管鳞状细胞癌（ESCC）的一线治疗。参加全球随机3期RATIONALE-306试验的晚期或转移性不可切除ESCC成年患者随机接受每3周200 mg的tislelizumab加ICC或匹配的安慰剂加ICC。对以TAP评分≥1%定义的PD-L1表达进行回顾性评估的患者进行疗效和安全性结果评估。结果：在初步分析数据截止日期（2022年2月28日），在替利利单抗加ICC组的230例患者（16.8[95%可信区间（CI） 15.3-20.8]个月）中观察到有临床意义的中位总生存期改善，而安慰剂加ICC组的248例患者[9.6 （95% CI 8.9-11.8）个月][分层风险比0.64 (95% CI 0.51-0.80)]；这一数据维持在3年随访数据截止日期（2023年11月24日）。在初步分析中，无进展生存期、客观缓解率、疾病控制率和缓解持续时间也观察到类似的结果。Tislelizumab + ICC是可耐受的，没有观察到新的安全性信号。结论：对于PD-L1 TAP评分≥1%的晚期或转移性不可切除ESCC患者，Tislelizumab + ICC是一种有效且耐受性良好的一线治疗选择。试验注册号：ClinicalTrials.gov NCT03783442。
First-Line Tislelizumab Plus Chemotherapy for Esophageal Squamous Cell Carcinoma with Programmed Death-Ligand 1 Expression ≥ 1%: A Retrospective Analysis of RATIONALE-306
Introduction
The United States Food and Drug Administration Oncologic Drugs Advisory Committee voted (September 2024) against the use of programmed cell death protein-1 inhibitors for first-line treatment of advanced or metastatic unresectable esophageal squamous cell carcinoma (ESCC) with a programmed death-ligand 1 (PD-L1) expression Tumor Area Positivity (TAP) score < 1% or combined positive score < 1 due to an unfavorable benefit–risk profile observed across the phase 3 CheckMate 648, KEYNOTE-590, and RATIONALE-306 trials. Therefore, we conducted a retrospective analysis of RATIONALE-306 to evaluate the efficacy and safety of tislelizumab plus investigator-chosen chemotherapy (ICC) versus placebo plus ICC in patients with advanced or metastatic unresectable ESCC and a PD-L1 TAP score ≥ 1%.
Methods
Adult patients with advanced or metastatic unresectable ESCC enrolled in the global, randomized, phase 3 RATIONALE-306 trial randomly received tislelizumab 200 mg every 3 weeks plus ICC or matched placebo plus ICC. Efficacy and safety outcomes were evaluated among patients who were retrospectively assessed for PD-L1 expression defined by a TAP score ≥ 1%.
Results
At primary analysis data cutoff (February 28, 2022), a clinically meaningful improvement in median overall survival was observed among 230 patients in the tislelizumab plus ICC arm {16.8 [95% confidence interval (CI) 15.3–20.8] months} versus 248 patients in the placebo plus ICC arm [9.6 (95% CI 8.9–11.8) months] [stratified hazard ratio 0.64 (95% CI 0.51–0.80)]; this was maintained at a 3-year follow-up data cutoff (November 24, 2023). Similar findings at primary analysis were observed for progression-free survival, objective response rate, disease control rate, and duration of response. Tislelizumab plus ICC was tolerable and no new safety signals were observed.
Conclusions
Tislelizumab plus ICC is an effective and well tolerated first-line treatment option for patients with advanced or metastatic unresectable ESCC and a tumor PD-L1 TAP score ≥ 1%.
期刊介绍：
Advances in Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of therapeutics and interventions (including devices) across all therapeutic areas. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged.
The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Advances in Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research.
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