Department of Oncology, CHUV, University of Lausanne, Lausanne, Switzerland; Faculty of Nursing, National and Kapodistrian University of Athens, Athens, Greece.
Departamento de Ciencias Médicas Básicas, Facultad de Medicina, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, Boadilla Del Monte, Madrid, 28668, Spain.
Eur J Cancer. 2021 Jan;142:63-82. doi: 10.1016/j.ejca.2020.10.014. Epub 2020 Nov 19.
Therapeutic cancer vaccination is an area of interest, even though promising efficacy has not been demonstrated so far.
A systematic review and meta-analysis was conducted to evaluate vaccines' efficacy on breast cancer (BC) and ovarian cancer (OC) patients. Our search was based on the PubMed electronic database, from 1st January 2000 to 4th February 2020.
response rate (ORR) was the primary end-point of interest, while progression-free survival (PFS), overall survival (OS) and toxicity were secondary end-points. Analysis was performed separately for BC and OC patients. Pooled ORRs were estimated by fixed or random effects models, depending on the detected degree of heterogeneity, for all studies with more than five patients. Subgroup analyses by vaccine type and treatment schema as well as sensitivity analyses, were implemented.
Among 315 articles initially identified, 67 were eligible for our meta-analysis (BC: 46, 1698 patients; OC: 32, 426 patients; where both BC/OC in 11). Dendritic-cell and peptide vaccines were found in more studies, 6/10 BC and 10/13 OC studies, respectively. In our primary BC analysis (21 studies; 428 patients), the pooled ORR estimate was 9% (95%CI[5%,13%]). The primary OC analysis (12 studies; 182 patients), yielded pooled ORR estimate of 4% (95%CI[1%,7%]). Similar were the results derived in sensitivity analyses. No statistically significant differences were detected by vaccine type or treatment schema. Median PFS was 2.6 months (95% confidence interval (CI)[1.9,2.9]) and 13.0 months (95%CI[8.5,16.3]) for BC and OC respectively, while corresponding median OS was 24.8 months (95%CI[15.0,46.0]) and 39.0 months (95%CI[31.0,49.0]). In almost all cases, the observed toxicity was only moderate.
Despite their modest results in terms of ORR, therapeutic vaccines in the last 20 years display relatively long survival rates and low toxicity. Since a plethora of different approaches have been tested, a better understanding of the underlying mechanisms is needed in order to further improve vaccine efficacy.
尽管目前尚未证明有疗效，但癌症治疗性疫苗仍是一个研究热点。
我们进行了一项系统评价和荟萃分析，以评估疫苗对乳腺癌（BC）和卵巢癌（OC）患者的疗效。我们的检索基于 PubMed 电子数据库，时间范围为 2000 年 1 月 1 日至 2020 年 2 月 4 日。
客观反应率（ORR）是主要的研究终点，而无进展生存期（PFS）、总生存期（OS）和毒性是次要研究终点。分别对 BC 和 OC 患者进行分析。对纳入的大于 5 例患者的所有研究，根据检测到的异质性程度，采用固定或随机效应模型来估计汇总 ORR。还进行了疫苗类型和治疗方案的亚组分析以及敏感性分析。
在最初确定的 315 篇文章中，有 67 篇符合我们的荟萃分析标准（BC：46 篇，1698 例患者；OC：32 篇，426 例患者；11 篇同时涉及 BC 和 OC）。树突状细胞疫苗和肽疫苗的研究较多，分别有 6/10 篇 BC 研究和 10/13 篇 OC 研究。在我们的主要 BC 分析（21 项研究；428 例患者）中，汇总的 ORR 估计值为 9%（95%CI[5%，13%]）。主要的 OC 分析（12 项研究；182 例患者）得出的汇总 ORR 估计值为 4%（95%CI[1%，7%]）。在敏感性分析中得到了相似的结果。未发现疫苗类型或治疗方案的统计学差异。BC 和 OC 的中位 PFS 分别为 2.6 个月（95%置信区间（CI）[1.9，2.9]）和 13.0 个月（95%CI[8.5，16.3]），相应的中位 OS 分别为 24.8 个月（95%CI[15.0，46.0]）和 39.0 个月（95%CI[31.0，49.0]）。在几乎所有情况下，观察到的毒性都只是中等程度。
尽管在 ORR 方面的结果较为温和，但过去 20 年来的治疗性疫苗显示出相对较长的生存率和较低的毒性。由于已经测试了多种不同的方法，因此需要更好地了解潜在的机制，以进一步提高疫苗的疗效。
