PDF(Pubmed)
Abstract：
Increased understanding of how the immune system regulates tumor growth has innovated the use of immunotherapeutics to treat various cancers. The impact of such therapies, including programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors, on the production of antidrug antibodies (ADAs) and their impact on outcomes, is poorly understood. This study aims to evaluate the clinical trial evidence on ADA incidence associated with PD-1, PD-L1, and CTLA-4 inhibitors in the treatment of cancer and to assess associations between treatment administered, ADA incidence, and treatment outcomes.
Embase®, Medline®, and EBM Reviews were searched via the OVID® platform on February 15, 2022. Conference proceedings, clinical trial registries, and global regulatory and reimbursement body websites were also searched. Eligible publications included clinical trials enrolling patients receiving cancer treatment with either PD-1, PD-L1, or CTLA-4 reporting outcomes including incidence or prevalence of ADAs and the impact of immunogenicity on treatment safety and efficacy. Reference lists of eligible publications were also searched. The review was conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and evidence quality assessment was conducted using the appropriate Joanna Briggs Institute Critical Appraisal tool.
After screening 4160 records and reviewing 97 full publications, a total of 34 publications reporting on 68 trials were included. A further 41 relevant clinical trials were identified on ClinicalTrials.gov and a further 32 from searches of packaging inserts. In total, 141 relevant trials covering 15 different checkpoint inhibitors and 16 different tumor types were included. Across the included trials, atezolizumab was associated with the highest incidence of ADAs (29.6% of 639 patients), followed by nivolumab (11.2% of 2,085 patients). Combination checkpoint inhibitor treatment appeared to increase the rate of ADAs versus monotherapy. Only 17 trials reported on the impact of ADAs on treatment outcomes with mixed results for the impact of ADAs on treatment efficacy, safety, and pharmacokinetics.
Checkpoint inhibitors for the treatment of cancer are immunogenic, with the incidence of treatment-emergent ADAs varying between individual therapies. It remains unclear what impact ADAs have on treatment outcomes.
Embase®, Medline®, and EBM Reviews were searched via the OVID® platform on February 15, 2022. Conference proceedings, clinical trial registries, and global regulatory and reimbursement body websites were also searched. Eligible publications included clinical trials enrolling patients receiving cancer treatment with either PD-1, PD-L1, or CTLA-4 reporting outcomes including incidence or prevalence of ADAs and the impact of immunogenicity on treatment safety and efficacy. Reference lists of eligible publications were also searched. The review was conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and evidence quality assessment was conducted using the appropriate Joanna Briggs Institute Critical Appraisal tool.
After screening 4160 records and reviewing 97 full publications, a total of 34 publications reporting on 68 trials were included. A further 41 relevant clinical trials were identified on ClinicalTrials.gov and a further 32 from searches of packaging inserts. In total, 141 relevant trials covering 15 different checkpoint inhibitors and 16 different tumor types were included. Across the included trials, atezolizumab was associated with the highest incidence of ADAs (29.6% of 639 patients), followed by nivolumab (11.2% of 2,085 patients). Combination checkpoint inhibitor treatment appeared to increase the rate of ADAs versus monotherapy. Only 17 trials reported on the impact of ADAs on treatment outcomes with mixed results for the impact of ADAs on treatment efficacy, safety, and pharmacokinetics.
Checkpoint inhibitors for the treatment of cancer are immunogenic, with the incidence of treatment-emergent ADAs varying between individual therapies. It remains unclear what impact ADAs have on treatment outcomes.
摘要：
背景：对免疫系统如何调节肿瘤生长的了解增加了免疫治疗剂在治疗各种癌症中的应用。这种疗法的影响，包括程序性细胞死亡蛋白1（PD-1）/程序性死亡配体1（PD-L1）和细胞毒性T淋巴细胞相关蛋白4（CTLA-4）抑制剂，关于抗药物抗体（ADAs）的产生及其对结果的影响，知之甚少。这项研究旨在评估与PD-1，PD-L1和CTLA-4抑制剂在癌症治疗中相关的ADA发生率的临床试验证据，并评估治疗之间的相关性。ADA发病率,和治疗结果。
方法：Embase®，Medline®,和EBM评论于2022年2月15日通过OVID®平台进行了搜索。会议记录，临床试验登记处，还搜索了全球监管和报销机构网站。符合条件的出版物包括接受PD-1，PD-L1或CTLA-4癌症治疗的患者的临床试验，报告结果包括ADAs的发生率或患病率以及免疫原性对治疗安全性和有效性的影响。还搜索了合格出版物的参考清单。根据系统审查和荟萃分析的首选报告项目进行审查和报告，并使用适当的JoannaBriggs研究所关键评估工具进行证据质量评估。
结果：在筛选了4160条记录和审查了97篇完整出版物之后，共纳入了68项试验的34篇出版物报告.在ClinicalTrials.gov上又确定了41项相关临床试验，在包装说明书的搜索中又确定了32项。总的来说,包括141项相关试验，涵盖15种不同的检查点抑制剂和16种不同的肿瘤类型。在包括的试验中，阿替珠单抗与ADAs的发病率最高（639例患者中为29.6%），其次是nivolumab(2,085例患者中的11.2%).与单一疗法相比，联合检查点抑制剂治疗似乎增加了ADAs的发生率。只有17个试验报告了ADAs对治疗结果的影响，但ADAs对治疗效果的影响结果参差不齐，安全,和药代动力学。
结论：用于治疗癌症的检查点抑制剂具有免疫原性，治疗中出现的ADAs的发生率在不同的治疗方法之间有所不同。目前尚不清楚ADAs对治疗结果有什么影响。
方法：Embase®，Medline®,和EBM评论于2022年2月15日通过OVID®平台进行了搜索。会议记录，临床试验登记处，还搜索了全球监管和报销机构网站。符合条件的出版物包括接受PD-1，PD-L1或CTLA-4癌症治疗的患者的临床试验，报告结果包括ADAs的发生率或患病率以及免疫原性对治疗安全性和有效性的影响。还搜索了合格出版物的参考清单。根据系统审查和荟萃分析的首选报告项目进行审查和报告，并使用适当的JoannaBriggs研究所关键评估工具进行证据质量评估。
结果：在筛选了4160条记录和审查了97篇完整出版物之后，共纳入了68项试验的34篇出版物报告.在ClinicalTrials.gov上又确定了41项相关临床试验，在包装说明书的搜索中又确定了32项。总的来说,包括141项相关试验，涵盖15种不同的检查点抑制剂和16种不同的肿瘤类型。在包括的试验中，阿替珠单抗与ADAs的发病率最高（639例患者中为29.6%），其次是nivolumab(2,085例患者中的11.2%).与单一疗法相比，联合检查点抑制剂治疗似乎增加了ADAs的发生率。只有17个试验报告了ADAs对治疗结果的影响，但ADAs对治疗效果的影响结果参差不齐，安全,和药代动力学。
结论：用于治疗癌症的检查点抑制剂具有免疫原性，治疗中出现的ADAs的发生率在不同的治疗方法之间有所不同。目前尚不清楚ADAs对治疗结果有什么影响。
