替雷利珠单抗联合化疗用于PD-L1肿瘤区域阳性评分≥5%的晚期或转移性食管鳞状细胞癌：RATIONALE-306的探索性、事后、长期随访
Tislelizumab plus chemotherapy for advanced or metastatic esophageal squamous-cell carcinoma in patients with PD-L1 Tumor Area Positivity score ≥5%: a post hoc, exploratory, long-term follow-up of RATIONALE-306☆.
作者
作者单位
- Department of Hepato-Gastroenterology, CHU de Poitiers, Poitiers, France.
- Department of Gastrointestinal Oncology, Fifth Medical Center, Chinese PLA General Hospital, Beijing, China.
- Department of Medical Oncology & Hematology, Groupe Hospitalier Paris Saint-Joseph, Paris, France.
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK.
- Department of Head and Neck, Esophageal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
- Department of Oncology and Radiotherapy, Maria Sklodowska-Curie National Cancer Research Institute, Warsaw, Poland.
- Digestive Oncology Division, University Hospitals Gasthuisberg, Leuven, Belgium; Digestive Oncology, KU Leuven, Leuven, Belgium.
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
- Department of Medical Oncology, Hospital Universitario Central de Asturias, ISPA, Oviedo, Spain.
- Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan.
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan.
- Experimental Clinical Abdominal Oncology Unit, Istituto Nazionale Tumori-IRCCS Fondazione G. Pascale, Naples, Italy.
- Department of Medical Oncology, Hospital Universitario Miguel Servet, Zaragoza, Spain.
- Global Statistics and Data Science, BeOne Medicines, Ltd, Ridgefield Park, USA.
- Clinical Development, BeOne Medicines, Ltd, Beijing, China.
- Clinical Biomarker, BeOne Medicines, Ltd, Beijing, China.
- Clinical Development, BeOne Medicines, Ltd, Shanghai, China.
- Department of Oncology, Mayo Clinic, Rochester, USA.
- Department of Medicine (Oncology, Gastroenterology, Hepatology, and Pulmonology), University of Leipzig Medical Center, Comprehensive Cancer Center Central Germany, Leipzig, Germany. Electronic address: florian.lordick@medizin.uni-leipzig.de.
摘要
中文
在随机、双盲、III期RATIONALE-306试验中，与安慰剂联合化疗相比，替雷利珠单抗联合化疗在意向治疗人群和PD-L1肿瘤区域阳性（TAP）评分≥5%亚组中，在中期分析和至少3年随访时均获得了有临床意义的总生存期（OS）获益。我们报告研究结束时的事后探索性长期结果，随访时间最短45.2个月，针对PD-L1 TAP评分≥5%的患者（依据欧洲药品管理局建议）。患者按1:1随机分配接受替雷利珠单抗200mg或安慰剂每3周一次，联合研究者选择的化疗。主要终点为OS。次要终点包括无进展生存期（PFS）、客观缓解率（ORR）、缓解持续时间（DoR）、安全性和生活质量（QoL）。在649例随机患者中，55.2%的PD-L1 TAP评分≥5%（替雷利珠单抗联合化疗n=172；安慰剂联合化疗n=186）。在最短45.2个月随访时，替雷利珠单抗联合化疗与安慰剂联合化疗相比改善了OS（中位19.1对10.0个月；HR 0.61）和PFS（中位8.2对5.5个月；HR 0.50）。ORR分别为71.5%对41.4%；中位DoR分别为7.1对5.4个月。两组QoL总体相似，替雷利珠单抗联合化疗在整体健康和疼痛缓解方面有更好趋势。任何级别治疗相关不良事件（TRAEs）发生率分别为97.7%（替雷利珠单抗联合化疗）对98.4%（安慰剂联合化疗），≥3级TRAEs分别为70.2%对66.5%。最常见的≥3级TRAEs为中性粒细胞计数降低（35.1%对31.9%）、贫血（13.5%对11.4%）和白细胞计数降低（12.3%对17.8%）。中期分析时两组间发生率差异≥5%的治疗期间不良事件在12个月后大幅减少。对于不可切除、局部晚期或转移性ESCC且PD-L1 TAP评分≥5%的患者，一线替雷利珠单抗联合化疗较安慰剂联合化疗提供了持续且有临床意义的疗效获益，且耐受性良好，无新的安全信号。
English
In the randomized, double-blind, phase III RATIONALE-306 trial, patients with unresectable, locally advanced, recurrent, or metastatic esophageal squamous-cell carcinoma (ESCC) treated with tislelizumab plus chemotherapy in the intent-to-treat population and in the programmed death-ligand 1 (PD-L1) Tumor Area Positivity (TAP) score ≥5% subgroup experienced clinically meaningful overall survival (OS) benefit compared with placebo plus chemotherapy at the interim analysis and minimum 3-year follow-up. We report post hoc, exploratory, longer-term outcomes at study closeout with minimum 45.2-month follow-up in patients with PD-L1 TAP score ≥5% per European Medicines Agency recommendation. Patients were randomly assigned (1 : 1) to receive tislelizumab 200 mg or placebo every 3 weeks plus investigator-chosen chemotherapy. The primary endpoint was OS. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), duration of response (DoR), safety, and quality of life (QoL). Of 649 randomly allocated patients, 55.2% had PD-L1 TAP score ≥5% (tislelizumab plus chemotherapy, n = 172; placebo plus chemotherapy, n = 186). At 45.2-month minimum follow-up, tislelizumab plus chemotherapy improved OS [median 19.1 versus 10.0 months; hazard ratio (HR) 0.61] and PFS (median 8.2 versus 5.5 months; HR 0.50) compared with placebo plus chemotherapy. ORR was 71.5% versus 41.4%; median DoR was 7.1 versus 5.4 months, respectively. QoL was similar overall between arms, with tislelizumab plus chemotherapy trending toward better global health and pain reduction. Any-grade treatment-related adverse events (TRAEs) occurred in 97.7% (tislelizumab plus chemotherapy) versus 98.4% (placebo plus chemotherapy) and grade ≥3 TRAEs in 70.2% versus 66.5%, respectively. The most common grade ≥3 TRAEs were decreased neutrophil count (35.1% versus 31.9%), anemia (13.5% versus 11.4%), and decreased white blood cell count (12.3% versus 17.8%). Treatment-emergent adverse events with ≥5% difference in incidence between arms at interim analysis decreased substantially after 12 months. First-line tislelizumab plus chemotherapy provided sustained and clinically meaningful efficacy benefits over placebo plus chemotherapy and was tolerable, with no new safety signals for patients with unresectable, locally advanced, or metastatic ESCC and PD-L1 TAP score ≥5%.
分类与指标
- 研究类型
- 临床研究
- 病种
- 食管癌
- JCR 分区
- Q1
- 影响因子
- 10.6
- 新锐分区
- 1区