替雷利珠单抗联合化疗与安慰剂联合化疗作为晚期胃或胃食管交界腺癌一线治疗的疗效比较：RATIONALE-305研究中的患者报告结局
Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first-line treatment of advanced gastric or gastroesophageal junction adenocarcinoma: patient-reported outcomes in the RATIONALE-305 study.
作者信息
Cruz-Correa Marcia, Xu Rui-Hua, Moehler Markus, Oh Do-Youn, Kato Ken, Spigel David, Arkenau Hendrik-Tobias, Tabernero Josep, Zimina Anastasia V, Bai Yuxian, Shi Jianhua, Lee Keun-Wook, Hirano Hidekazu, Wyrwicz Lucjan, Cid Roberto Pazo, Xu Hui, Sheng Tao, Barnes Gisoo
机构信息
University of Puerto Rico, School of Medicine, San Juan, Puerto Rico and Pan American Center for Oncology Trials, San Juan, Puerto Rico.
Department of Medical Oncology, Collaborative Innovation Center of Cancer Medicine, University Cancer Center State Key Laboratory of Oncology in South China, Guangzhou, China.
出版信息
Curr Med Res Opin. 2025 Jun;41(6):1007-1016. doi: 10.1080/03007995.2025.2501588. Epub 2025 Jun 18.
OBJECTIVE
RATIONALE-305 (NCT03777657) demonstrated that tislelizumab plus chemotherapy statistically improved overall survival versus placebo plus chemotherapy as first-line treatment in patients with advanced gastric/gastroesophageal junction adenocarcinoma (GC/GEJC). This analysis examined patient-reported outcomes (PROs) at final analysis.
METHODS
Adults with previously untreated, unresectable, or metastatic GC/GEJC were randomized (1:1) to tislelizumab or placebo intravenously once every 3 weeks plus chemotherapy. PROs assessed health-related quality of life (HRQoL) using EORTC QLQ-C30 and EORTC QLQ-STO22. A mixed model for repeated measures was used for PRO endpoints at treatment cycles 4 and 6, and time to deterioration was analyzed.
RESULTS
Tislelizumab arm had improved outcomes over placebo arm in least-squares (LS) mean change from baseline to cycle 6 for QLQ-C30 global health status/quality of life (GHS/QoL) (LS mean difference, 2.52 [95% CI: 0.29-4.74]), physical functioning (2.46 [0.49-4.43]), fatigue (-3.01 [-5.78 to -0.24]), and STO22 index score (-1.62 [-3.12 to -0.12]) as well as maintenance of upper gastrointestinal symptoms (-1.74 [-3.55-0.06]) and pain/discomfort (-1.88 [-4.03-0.27]). Patients receiving tislelizumab plus chemotherapy had a lower risk for deterioration of GHS/QoL (hazard ratio 0.77 [95% CI: 0.60-0.98]), physical functioning (0.72 [0.57-0.92]), STO22 index score (0.64 [0.45-0.92]), pain/discomfort (0.74 [0.58-0.96]), and upper gastrointestinal symptoms (0.73 [0.56-0.95]).
CONCLUSIONS
Advanced GC/GEJC patients treated with tislelizumab plus chemotherapy versus placebo plus chemotherapy in first-line had sustained and improved HRQoL. These results, along with previous efficacy and safety data, support tislelizumab plus chemotherapy as a first-line treatment option for GC/GEJC.
TRIAL REGISTRATION
The RATIONALE-305 trial is registered on ClinicalTrials.gov (ClinicalTrials.gov identifier: NCT03777657).ClinicalTrials.gov identifier: NCT03777657.
目的
RATIONALE-305（NCT03777657）研究表明，对于晚期胃/胃食管交界腺癌（GC/GEJC）患者，替雷利珠单抗联合化疗作为一线治疗方案，与安慰剂联合化疗相比，在统计学上显著改善了总生存期。本分析在最终分析时考察了患者报告结局（PRO）。
方法
将既往未接受过治疗、不可切除或转移性GC/GEJC的成人患者按1:1随机分组，每3周静脉注射一次替雷利珠单抗或安慰剂加化疗。PRO使用欧洲癌症研究与治疗组织（EORTC）QLQ-C30和EORTC QLQ-STO22评估健康相关生活质量（HRQoL）。采用重复测量混合模型分析治疗周期4和6时的PRO终点，并分析恶化时间。
结果
在QLQ-C30全球健康状况/生活质量（GHS/QoL）从基线到第6周期的最小二乘（LS）平均变化方面，替雷利珠单抗组的结局优于安慰剂组（LS平均差异为2.52 [95%置信区间：0.29 - 4.74]），身体功能（2.46 [0.49 - 4.43]）、疲劳（-3.01 [-5.78至-0.24]）、STO22指数评分（-1.62 [-3.12至-0.12]）以及上消化道症状的维持（-1.74 [-3.55 - 0.06]）和疼痛/不适（-1.88 [-4.03 - 0.27]）。接受替雷利珠单抗联合化疗的患者GHS/QoL恶化风险较低（风险比0.77 [95%置信区间：0.60 - 0.98]），身体功能（0.72 [0.57 - 0.92]）、STO22指数评分（0.64 [0.45 - 0.92]）、疼痛/不适（0.74 [0.58 - 0.96]）和上消化道症状（0.73 [0.56 - 0.95]）。
结论
一线接受替雷利珠单抗联合化疗对比安慰剂联合化疗治疗的晚期GC/GEJC患者，其HRQoL得到持续改善。这些结果与之前的疗效和安全性数据一起，支持替雷利珠单抗联合化疗作为GC/GEJC的一线治疗选择。
试验注册
RATIONALE-305试验已在ClinicalTrials.gov注册（ClinicalTrials.gov标识符：NCT03777657）。ClinicalTrials.gov标识符：NCT037
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