新辅助/辅助帕博利珠单抗联合化疗在局部进展期胃或胃食管结合部腺癌中的疗效及安全性:KEYNOTE-585研究的期中分析解读  

Interpretation of an Interim Analysis of the KEYNOTE-585 Study:Efficacy and Safety of Neoadjuvant/Adjuvant Pembrolizumab plus Chemotherapy in Locally-Advanced Gastric or Gastroesophageal Junction Adenocarcinoma

作　　者：黄兴茂 褚嘉栋 俞鹏飞[1] HUANG Xingmao;CHU Jiadong;YU Pengfei(Zhejiang Cancer Hospital,Hangzhou Institute of Medicine(HIM),Chinese Academy of Sciences,Hangzhou 310022,China)

机构地区：[1]浙江省肿瘤医院,中国科学院杭州医学研究所,浙江杭州310022

出　　处：《肿瘤学杂志》2024年第4期344-351,共8页Journal of Chinese Oncology

摘　　要：对于局部进展期可切除的胃或胃食管结合部腺癌(gastric or gastroesophageal junction adenocarcinoma,GC/GEJC),联合新辅助/辅助化疗和免疫检查点抑制剂的获益尚不清楚。KEYNOTE-585研究的期中分析结果 报告了新辅助/辅助帕博利珠单抗联合化疗在局部进展期可切除GC/GEJC患者中的疗效及安全性。研究者在24个国家的143个中心进行了一项随机双盲、安慰剂对照3期临床研究。研究招募了年龄≥18岁、既往未经治疗且可切除的局部进展期GC/GEJC患者(≥T_(3)或N+)。研究分为两个队列,主要队列纳入804例,FLOT队列纳入203例。患者入组后按1∶1随机分为试验组和对照组,并基于地区(亚洲vs非亚洲)、肿瘤分期(Ⅱ vs Ⅲ vs Ⅳa)、化疗方案(XP/FP vs FLOT)进行分层。主要终点设置为病理完全缓解率、无事件生存期、总生存期以及安全性(FLOT队列)。该研究已在ClinicalTrial.gov注册(编号NCT03221426),目前已完成招募。在2017年10月9日至2021年1月25日期间,1 007例患者1∶1随机纳入帕博利珠单抗+化疗组(n=502)和安慰剂+化疗组(n=505)。主要队列中位随访47.7个月后,帕博利珠单抗+化疗组相比安慰剂+化疗组病理完全缓解率显著提升10.9%(P<0.001);无事件生存期有所增加但未达到预设统计学显著水平[44.4个月(95%CI:33.0~NR) vs 25.3个月(95%CI:20.6~33.9),HR=0.81,95%CI:0.67~0.99,P=0.019 8];总生存期无明显获益(60.7个月vs 58.0个月,HR=0.90,95%CI:0.73~1.12,P=0.174)。此外,两组安全性事件方面相似,包括3级及以上不良事件(78%vs 74%)和治疗相关严重不良事件(26% vs 24%)发生率。在未经治疗的局部进展期GC/GEJC患者中,新辅助/辅助帕博利珠单抗联合化疗可显著提高pCR率,但未能显著转化为EFS/OS生存获益。The benefit of chemotherapy plus immune checkpoint inhibitors as neoadjuvant/adjuvant therapy in locallyadvanced gastric or gastroesophageal junction adenocarcinoma(GC/GEJC) is unknown.The interim analysis of the KEYNOTE-585 reported the efficacy and safety of neoadjuvant/adjuvant pembrolizumab plus chemotherapy in patients with locally-advanced GC/GEJC.The investigators conducted a randomized,double-blind,placebo-controlled phase 3 clinical trial at 143 centers in 24 countries.The study recruited patients with age ≥ 18 years old,previously untreated and resectable locally-advanced GC/GEJC(≥T_(3) or N+).The study was divided into two cohorts,with 804 patients included in the main cohort and 203 patients in the FLOT cohort.Patients were enrolled and randomized 1 ∶1 into treatment and control groups.Randomization was stratified by region(Asia vs non-Asia),tumor stage(Ⅱ vs Ⅲ vs Ⅳa),and chemotherapy regimen(XP/FP vs FLOT).The primary endpoints were pathological complete response(pCR),event-free survival,overall survival,and safety(FLOT cohort).The study was registered with ClinicalTrial.gov(No.NCT03221426) and recruitment has been completed.Between October 9,2017 and January 25,2021,1 007 patients were randomized 1∶1 to the pembrolizumab plus chemotherapy group(n=502) and the placebo plus chemotherapy group(n=505).After a median follow-up of 47.7 months in the primary cohort,the treatment group significantly improved the pCR rate by10.9% compared to the placebo group(P<0.001);event-free survival was increased but did not reach the pre-specified statistically significant level [44.4 months(95%CI:33.0~NR) vs 25.3 months(95%CI:20.6~33.9),HR=0.81,95% CI:0.67~0.99,P=0.019 8];no significant benefit in overall survival(60.7 months vs 58.0 months,HR=0.90,95%CI:0.73 ~1.12,P =0.174).In addition,there is similar incidence of safety events in the two groups,including adverse events grade≥3(78% vs 74%) and treatment-related serious adverse events(26% vs 24%).In untreated patients with locally-advanced GC/GEJC,neoa

关 键 词：胃肿瘤 胃食管结合部腺癌 帕博利珠单抗 病理完全缓解率 无事件生存期 总生存期 

分 类 号：R735[医药卫生—肿瘤]