Tislelizumab加化疗治疗程序性死亡-配体1表达≥1%的晚期胃癌：RATIONALE-305的回顾性分析

IF 3.4 3区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in Therapy Pub Date : 2025-03-13 DOI:10.1007/s12325-025-03133-7

Markus Moehler, Do-Youn Oh, Ken Kato, Tobias Arkenau, Josep Tabernero, Keun-Wook Lee, Sun Young Rha, Hidekazu Hirano, David Spigel, Kensei Yamaguchi, Lucjan Wyrwicz, Umut Disel, Roberto A. Pazo-Cid, Lorenzo Fornaro, Yaling Xu, Tao Sheng, Silu Yang, Alysha Kadva, Marcia Cruz-Correa, Rui-Hua Xu

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引用次数: 0

摘要

介绍：Tislelizumab加研究者选择化疗（ICC）在rational -305中，在意图治疗人群中局部晚期不可切除或转移性人表皮生长因子受体2 （HER2）阴性胃癌/胃食管结癌（GC/GEJC）患者和程序死亡配体1 （PD-L1）肿瘤区域阳性（TAP）评分≥5%的患者中，与安慰剂加ICC相比，总体生存率（OS）有统计学显著改善。美国食品和药物管理局肿瘤药物咨询委员会（2024年9月）投票反对在PD-L1联合阳性评分患者中使用程序性细胞死亡蛋白-1抑制剂进行一线治疗。方法：患有局部晚期不可切除或转移性her2阴性GC/GEJC的成年患者每3周随机接受200 mg tislelizumab或安慰剂与ICC。在PD-L1 TAP评分≥1%的患者中，回顾性评估tislelizumab加ICC与安慰剂加ICC的疗效和安全性。结果：在最终分析截止日期（2023年2月28日），432例患者接受tislelizumab + ICC治疗，453例接受安慰剂+ ICC治疗，PD-L1 TAP评分≥1%。与安慰剂加ICC相比，tislelizumab加ICC对OS有临床意义的改善[分别为15.0个月（95%可信区间[CI] 13.3-16.7）和12.8个月（95% CI 12.1-14.1）；分层风险比0.77 （95% CI 0.67-0.90）。无进展生存期、总缓解率、缓解持续时间和疾病控制率也得到改善。操作系统的改进维持在3年的数据截止日期（2024年2月28日）。Tislelizumab + ICC具有可接受的安全性，没有新的安全信号。结论：对于PD-L1 TAP评分≥1%的局部晚期不可切除或转移性her2阴性GC/GEJC患者，Tislelizumab + ICC是一种有效且耐受的一线治疗方法。试验注册号：NCT03777657。

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First-Line Tislelizumab Plus Chemotherapy for Advanced Gastric Cancer with Programmed Death-Ligand 1 Expression ≥ 1%: A Retrospective Analysis of RATIONALE-305

Introduction

Tislelizumab plus investigator-chosen chemotherapy (ICC) demonstrated a statistically significant improvement in overall survival (OS) versus placebo plus ICC in RATIONALE-305 in patients with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric cancer/gastroesophageal junction cancer (GC/GEJC) in the intent-to-treat population and in patients with programmed death-ligand 1 (PD-L1) Tumor Area Positivity (TAP) score ≥ 5%. The United States Food and Drug Administration Oncologic Drugs Advisory Committee voted (September 2024) against first-line treatment with programmed cell death protein-1 inhibitors in this setting in patients with a PD-L1 combined positive score < 1 or TAP score < 1%, due to an unfavorable benefit–risk profile. Thus, we retrospectively analyzed data from RATIONALE-305 in patients with a PD-L1 TAP score ≥ 1%.

Methods

Adult patients with locally advanced unresectable or metastatic HER2-negative GC/GEJC were randomized to tislelizumab 200 mg or placebo with ICC every 3 weeks. Efficacy and safety outcomes of tislelizumab plus ICC versus placebo plus ICC were retrospectively assessed in those with a PD-L1 TAP score ≥ 1%.

Results

At the final analysis cutoff (February 28, 2023), 432 patients received tislelizumab plus ICC and 453 received placebo plus ICC, and had a PD-L1 TAP score ≥ 1%. Clinically meaningful improvements to OS were observed with tislelizumab plus ICC compared with placebo plus ICC [15.0 months (95% confidence interval [CI] 13.3–16.7) vs. 12.8 months (95% CI 12.1–14.1), respectively; stratified hazard ratio 0.77 (95% CI 0.67–0.90)]. Progression-free survival, overall response rate, duration of response, and disease control rate, were also improved. OS improvements were maintained at a 3-year data cutoff (February 28, 2024). Tislelizumab plus ICC had an acceptable safety profile with no new safety signals.

Conclusions

Tislelizumab plus ICC is an effective and tolerable first-line treatment for patients with locally advanced unresectable or metastatic HER2-negative GC/GEJC with a PD-L1 TAP score ≥ 1%.

Trial registration number

NCT03777657.

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来源期刊

Advances in Therapy 医学-药学

CiteScore

7.20

自引率

2.60%

发文量

353

审稿时长

6-12 weeks

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.