Shaoyi Chen, Zewen Sun, Yun Li, Fan Yang, Peiyu Wang, Kezhong Chen, Jun Wang, Mantang Qiu
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The primary outcome was overall survival (OS), with progression-free survival (PFS) as secondary outcome. Treatment-related adverse events (TRAEs) was the major safety outcome. Random-effects model was employed in this meta-analysis. Risk of bias was evaluated with RoB 2.</p><p><strong>Findings: </strong>Eleven RCTs comprising 3228 patients (67% male, n = 2162) were included, without high risk of bias. The included studies involved employing cancer vaccines as first-line maintenance therapy, second-line therapy, or third-line therapy. In general, Cancer vaccines associated with improved OS (HR = 0.85, 95% CI, 0.78-0.92, <i>P</i> < 0.001) but did not significantly improve PFS (HR = 0.91, 95% CI, 0.79-1.05, <i>P</i> = 0.195). Subgroup analyses indicated better OS for patients with ECOG = 1, first-line chemotherapy, squamous cell carcinoma, stable disease after first-line therapy, stage IV, and smoking history. 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引用次数: 0
摘要
背景：尽管有大量关于癌症疫苗的随机对照试验（rct），但对一线治疗后晚期非小细胞肺癌（NSCLC）患者的有效性和安全性的系统评估仍然缺乏。方法：在本系统评价和荟萃分析（PROSPERO, CRD42024568178）中，检索PubMed、Cochrane Library和Embase数据库，检索时间从建库到2024年12月27日。已发表的II期或III期随机对照试验报告了一线治疗后接受疫苗治疗的晚期或转移性NSCLC患者的生存结果。数据由两位审稿人独立提取。主要终点是总生存期（OS），次要终点是无进展生存期（PFS）。治疗相关不良事件（TRAEs）是主要的安全性指标。本meta分析采用随机效应模型。偏倚风险用RoB 2评价。结果：纳入11项随机对照试验，共3228例患者（67%为男性，n = 2162），无高偏倚风险。纳入的研究包括采用癌症疫苗作为一线维持治疗、二线治疗或三线治疗。总体而言，癌症疫苗与改善OS相关（HR = 0.85, 95% CI, 0.78-0.92, P < 0.001），但未显著改善PFS （HR = 0.91, 95% CI, 0.79-1.05, P = 0.195）。亚组分析显示，ECOG = 1、一线化疗、鳞状细胞癌、一线治疗后病情稳定、IV期和吸烟史的患者有更好的OS。鳞状细胞癌（HR = 0.74, 95% CI, 0.61-0.90, P = 0.003）对疫苗治疗的反应优于腺癌（HR = 0.83, 95% CI, 0.55-1.26, P = 0.377）。TRAEs的合并OR为1.5 （95% CI, 0.63-3.61, P = 0.361）。探索性分析表明，对癌症疫苗的免疫反应可作为疫苗效果的预测性生物标志物。此外，当meta分析针对一线维持治疗时，基于7项试验获得了一致的疗效和安全性结果。这项荟萃分析证明了癌症疫苗在一线治疗后晚期NSCLC患者的临床疗效和安全性，特别是在鳞状细胞癌患者中。免疫反应被确定为疫苗效果的预测性生物标志物。本研究为癌症疫苗在一线治疗后晚期非小细胞肺癌患者中的临床应用提供了最新证据。资助项目：20240484580、20230484314、2023YFF0723500、2021RU002、82173386、RZ2022-04。
Evaluation of clinical and safety outcomes of cancer vaccines in patients with advanced non-small cell lung cancer after first-line therapy: a systematic review and meta-analysis.
Background: Despite numerous randomized controlled trials (RCTs) on cancer vaccines, systematic evaluations of their efficacy and safety for patients with advanced non-small cell lung cancer (NSCLC) following first-line therapy remain lacking.
Methods: In this systematic review and meta-analysis (PROSPERO, CRD42024568178), PubMed, Cochrane Library, and Embase databases were searched from inception up to December 27, 2024. Published phase II or III RCTs reporting survival outcomes in advanced or metastatic NSCLC patients who received vaccine therapy after first-line therapy were included. Data were independently extracted by two reviewers. The primary outcome was overall survival (OS), with progression-free survival (PFS) as secondary outcome. Treatment-related adverse events (TRAEs) was the major safety outcome. Random-effects model was employed in this meta-analysis. Risk of bias was evaluated with RoB 2.
Findings: Eleven RCTs comprising 3228 patients (67% male, n = 2162) were included, without high risk of bias. The included studies involved employing cancer vaccines as first-line maintenance therapy, second-line therapy, or third-line therapy. In general, Cancer vaccines associated with improved OS (HR = 0.85, 95% CI, 0.78-0.92, P < 0.001) but did not significantly improve PFS (HR = 0.91, 95% CI, 0.79-1.05, P = 0.195). Subgroup analyses indicated better OS for patients with ECOG = 1, first-line chemotherapy, squamous cell carcinoma, stable disease after first-line therapy, stage IV, and smoking history. Squamous cell carcinoma (HR = 0.74, 95% CI, 0.61-0.90, P = 0.003) responded better to vaccine therapy than adenocarcinoma (HR = 0.83, 95% CI, 0.55-1.26, P = 0.377). The pooled OR for TRAEs was 1.5 (95% CI, 0.63-3.61, P = 0.361). Exploratory analysis indicated that immune response to cancer vaccines may serve as a predictive biomarker for vaccines effect. Besides, consistent efficacy and safety results were obtained when the meta-analysis was specific to first-line maintenance therapy based on seven trials.
Interpretation: This meta-analysis demonstrated the clinical efficacy and safety of cancer vaccines in advanced NSCLC patients after first-line therapy, especially in those with squamous cell carcinoma. Immune response was identified as a predictive biomarker for vaccines effect. This study provides the state-of-the-art evidence for the clinical application of cancer vaccines in advanced NSCLC patients after first-line therapy.
期刊介绍：
eClinicalMedicine is a gold open-access clinical journal designed to support frontline health professionals in addressing the complex and rapid health transitions affecting societies globally. The journal aims to assist practitioners in overcoming healthcare challenges across diverse communities, spanning diagnosis, treatment, prevention, and health promotion. Integrating disciplines from various specialties and life stages, it seeks to enhance health systems as fundamental institutions within societies. With a forward-thinking approach, eClinicalMedicine aims to redefine the future of healthcare.
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