Liu Hua, Wang Yakun, Qi Changsong, Xie Tong, Peng Zhi, Li Jian, Shen Lin, Zhang Xiaotian
Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China.
Front Oncol. 2022 Apr 7;12:835389. doi: 10.3389/fonc.2022.835389. eCollection 2022.
Gastric cancer (GC) is one of the most common malignant cancers worldwide. The development of potential antitumor agents is being investigated and stimulates more clinical trials. Overall survival (OS) is consistently considered the primary endpoint for clinical trials on treatment effect assessment. However, finding an appropriate endpoint more sensitive and easy for trials is vital. For adjuvant chemotherapy, current evidence has shown that disease-free survival (DFS) could be a surrogate endpoint for randomized controlled trials (RCTs) with GC, but evidence for neoadjuvant chemotherapy (NCT) or chemoradiotherapy (NCRT) is inadequate. This study was designed to evaluate the possibility that event-free survival (EFS) surrogates OS in RCTs of NCT/NCRT of gastric orss gastroesophageal (GC or GEJ) adenocarcinoma patients (ADK).
A literature search was conducted through databases including PubMed, the Cochrane Library, and Embase. References and articles from other sources were also included. A total of 8 RCTs with 2,837 patients were eventually analyzed. Hazard ratios (HRs) of OS and EFS were directly approached. The surrogacy of EFS was assessed through the correlation of determination R. We used Review Manage pooling HRs of OS and EFS at the trial level. I was used to demonstrate the heterogeneity of inclusions. Publication bias was summarized and illustrated through funnel plots. All analyses were on two sides with a setting statistical significance as p < 0.05.
Eight RCTs of 2,837 patients were analyzed at the trial level. The I for OS was 21% and 51% for EFS, and a fixed-effect model was used. The pooled HR of OS was 0.83 (95% CI: 0.75-0.92, p < 0.001), and that of EFS was 0.78 (95% CI: 0.71-0.86, p < 0.001). The regression correlation coefficient between EFS and OS was 0.76 (95% CI: 0.41-1.11, p = 0.002), and the coefficient of determination R = 0.826.
A strong correlation was observed between OS and EFS at the trial level. EFS could be a surrogate endpoint for neoadjuvant RCTs of GC and GEJ adenocarcinoma. Further studies and evidence from individual data are expected.
胃癌（GC）是全球最常见的恶性肿瘤之一。正在研究潜在抗肿瘤药物的开发，并推动了更多的临床试验。总生存期（OS）一直被视为评估治疗效果的临床试验的主要终点。然而，找到一个对试验更敏感且更易于操作的合适终点至关重要。对于辅助化疗，目前的证据表明无病生存期（DFS）可能是GC随机对照试验（RCT）的替代终点，但新辅助化疗（NCT）或放化疗（NCRT）的证据不足。本研究旨在评估在胃或食管胃交界部（GC或GEJ）腺癌患者（ADK）的NCT/NCRT的RCT中无事件生存期（EFS）替代OS的可能性。
通过包括PubMed、Cochrane图书馆和Embase在内的数据库进行文献检索。还纳入了其他来源的参考文献和文章。最终分析了8项RCT，共2837例患者。直接计算OS和EFS的风险比（HR）。通过决定系数R的相关性评估EFS的替代作用。我们在试验层面使用Review Manage汇总OS和EFS的HR。I用于证明纳入研究的异质性。通过漏斗图总结和说明发表偏倚。所有分析均为双侧，设定统计学显著性为p<0.05。
在试验层面分析了8项RCT，共2837例患者。OS的I为21%，EFS的I为51%，采用固定效应模型。OS的汇总HR为0.83（95%CI：0.75-0.92，p<0.001），EFS的汇总HR为0.78（95%CI：0.71-0.86，p<0.001）。EFS与OS之间的回归相关系数为0.76（95%CI：0.41-1.11，p=0.002），决定系数R=0.826。
在试验层面观察到OS与EFS之间存在强相关性。EFS可能是GC和GEJ腺癌新辅助RCT的替代终点。期待进一步的研究和来自个体数据的证据。
