帕博利珠单抗治疗晚期胃腺癌、胃食管结合部腺癌患者的疗效与安全性——Keynote-061/062研究阴性结果解读  

Efficacy and Safety of Pembrolizumab in Advanced Gastric Adenocarcinoma and Adenocarcinoma at the Gastroesophageal Junction: Interpretation of Negative Results in Keynote-061/062 Study

作　　者：李梦雅 周佳薇 仲子航 李卫[1] CSCO统计专家委员会Keynote工作组 LI Meng-ya;ZHOU Jia-wei;ZHONG Zi-hang;LI Wei;The CSCO Statistical Expert Committee Keynote Group(Department of Medical Statistics,Fuwai Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College/National Center for Cardiovascular Diseases,Beijing 102308,China;School of Public Health,Nanjing Medical University,Nanjing 211166,China;不详)

机构地区：[1]北京协和医学院/中国医学科学院/阜外医院/国家心血管病中心医学统计部,北京102308 [2]南京医科大学公共卫生学院,江苏南京211166 [3]不详

出　　处：《肿瘤学杂志》2022年第7期614-623,共10页Journal of Chinese Oncology

摘　　要：探索帕博利珠单抗(Pembrolizumab)与紫杉醇比较在PD-L1阳性晚期胃/胃食管结合部腺癌临床疗效和安全性的两项全球多中心、随机对照、Ⅲ期研究(Keynote-061和062)均以失败告终,导致FDA撤销了Keytruda(可瑞达)在该适应证上的应用。两项研究样本量分别为592例和763例,主要终点均为总生存(overall survival,OS)。结果显示:帕博利珠单抗单药对比紫杉醇二线治疗PD-L1联合阳性分数(combined positive score,CPS)≥1患者中两组中位总生存期分别为9.1个月和8.3个月,风险比(hazard ratio,HR)为0.82 (95%CI:0.66~1.03,P=0.042 1),中位无进展生存期(progression-free survival,PFS)分别为1.5个月和4.1个月,风险比为1.27(95%CI:1.03~1.57);一线治疗的患者(CPS1)帕博利珠单抗OS非劣效于化疗,HR为0.91(99.2%CI:0.69~1.18),PFS风险比为1.66(95%CI:1.37~2.01);帕博利珠单抗联合化疗组相比化疗疗效改善没有明显优势,OS风险比为0.85 (95%CI:0.70~1.03);PFS风险比为0.84(95%CI:0.70~1.02)。但在安全性方面,帕博利珠单抗相对于化疗均表现出较好的安全性。帕博利珠单抗单药在晚期胃/胃食管结合部腺癌的研究结果为阴性,其研究策略、方案设计、统计分析、后续布局等均值得进一步讨论和思考。Two global multicentral, randomized controlled, phase Ⅲ studies(Keynote 061 and Keynote 062)exploring the clinical efficacy and safety of pembrolizumab in PD-L1 positive advanced gastric/gastroesophageal junction adenocarcinoma patients ended in failure, leading the US Food and Drug Administration to withdraw Keytruda for this indication. The sample sizes of the two studies were 592 and 763 subjects, respectively, and the primary endpoint was overall survival(OS). The results showed that the median overall survival was 9.1 months and 8.3 months, respectively for pembrolizumab alone versus paclitaxel as second-line therapy(HR =0.82, 95% CI: 0.66 ~1.03;P =0.042 1) and median progression-free survival was 1.5 months for pembrolizumab and 4.1 months for paclitaxel(HR=1.27, 95%CI: 1.03~1.57) in CPS1 patients;the OS of pembrolizumab was non-inferior to chemotherapy as first-line treatment(CPS1), with HR=0.91(99.2%CI: 0.69~1.18), whereas, for PFS the HR was 1.66(95% CI: 1.37 ~2.01). Pembrolizumab in combination with chemotherapy had no significant improvement over chemotherapy(OS: HR=0.85, 95%CI: 0.70~1.03;PFS:HR=0.84, 95%CI: 0.70~1.02). But pembrolizumab showed better safety than chemotherapy. Although the research results of advanced gastric/gastroesophageal junction carcinoma is negative, its research strategy, protocol design, statistical analysis and subsequent layout are worthy of further discussion and consideration.

关 键 词：帕博利珠单抗 胃腺癌 胃食管结合部腺癌 临床试验 阴性结果 

分 类 号：R735.2[医药卫生—肿瘤]