免疫相关不良事件与纳武利尤单抗/紫杉醇联合免疫检查点抑制剂相关：系统评价和网络荟萃分析。
Immune-related adverse events associated with nab-paclitaxel/paclitaxel combined with immune checkpoint inhibitors: a systematic review and network meta-analysis.
机构信息
Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, Fudan University, Shanghai, China.
School of Pharmacy, Minhang Hospital, Fudan University, Shanghai, China.
出版信息
Front Immunol. 2023 Jul 14;14:1175809. doi: 10.3389/fimmu.2023.1175809. eCollection 2023.
OBJECTIVE
The combination of nanoparticle albumin-bound paclitaxel (nab-PTX)/paclitaxel (PTX) with immune checkpoint inhibitors (ICIs) has demonstrated significant efficacy in cancer patients. However, the safety of these combination regimens remains conflicting in former researches. Therefore, in order to address this issue, we performed a systematic review and network meta-analysis (NMA) to evaluate and compare the safety profile.
METHODS
We performed a systematic review by searching randomized controlled trials (RCTs) from PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, and Web of Science up to August 15, 2022. The primary outcomes were all-grade (grade 1-5) and high-grade (grade 3-5) immune-related adverse events (irAEs). Secondary outcomes were all-grade (grade 1-5) and high-grade (grade 3-5) irAEs of subgroups of ICIs.
RESULTS
There were 22 RCTs included in the NMA, involving a total of 15 963 patients diagnosed with any type of cancer. ICIs+nab-PTX was associated with a noticeably decreased risk of grade 3-5 pneumonitis (odds ratio [OR]=0.28, 95% credible interval [CrI]: 0.09,0.90) compared to ICI monotherapy; ICIs+PTX showed a lower risk of grade 1-5 hyperthyroidism (OR=0.46, 95% CrI: 0.22-0.96) and grade 1-5 hypothyroidism (OR=0.49, 95% CrI: 0.26-0.93) than ICIs. Compared with PD-1, PD-1+PTX was associated with a statistically significantly lower risk of grade 1-5 pneumonitis (OR=0.32, 95% CrI: 0.11-0.92). PD-L1 resulted in a noticeably lower risk of grade 1-5 hypothyroidism (OR=0.34, 95% CrI: 0.12-1.00) than PD-L1+PTX. Nearly all treatment regimens containing ICIs demonstrated significantly higher risks of irAEs compared to the standard chemotherapy groups.
CONCLUSION
Nab-PTX/PTX+ICIs demonstrated an approach leading to decreased risk of irAEs compared with ICI monotherapy. This finding supports that ICIs+nab-PTX/PTX may be a safer treatment strategy. Moreover, we also found that the combination regimens containing ICIs had a higher risk of irAEs than standard chemotherapy. Additionally, ICIs+nab-PTX demonstrated a decreased risk of irAEs compared to ICIs+PTX. PD-1 inhibitors were associated with a higher risk of irAEs than PD-L1 inhibitors.
目的
纳米白蛋白结合紫杉醇（nab-PTX）/紫杉醇（PTX）与免疫检查点抑制剂（ICIs）联合使用在癌症患者中显示出显著疗效。然而，这些联合方案的安全性在前瞻性研究中仍存在争议。因此，为了解决这个问题，我们进行了系统评价和网络荟萃分析（NMA），以评估和比较安全性概况。
方法
我们对截至 2022 年 8 月 15 日PubMed、EMBASE、Cochrane 图书馆、ClinicalTrials.gov 和 Web of Science 中的随机对照试验（RCT）进行了系统评价。主要结局是所有级别（1-5 级）和高级别（3-5 级）免疫相关不良事件（irAEs）。次要结局是各亚组 ICIs 的所有级别（1-5 级）和高级别（3-5 级）irAEs。
结果
NMA 共纳入 22 项 RCT，共纳入 15963 例任何类型癌症患者。与 ICI 单药治疗相比，ICIs+nab-PTX 显著降低了 3-5 级肺炎的风险（比值比 [OR] = 0.28，95%可信区间 [CrI]：0.09，0.90）；与 ICI 相比，ICIs+PTX 降低了 1-5 级甲状腺功能亢进症（OR = 0.46，95% CrI：0.22-0.96）和 1-5 级甲状腺功能减退症（OR = 0.49，95% CrI：0.26-0.93）的风险。与 PD-1 相比，PD-1+PTX 与 1-5 级肺炎的风险显著降低相关（OR = 0.32，95% CrI：0.11-0.92）。PD-L1 导致 1-5 级甲状腺功能减退症的风险明显降低（OR = 0.34，95% CrI：0.12-1.00），而 PD-L1+PTX 则不然。与标准化疗组相比，几乎所有含有 ICI 的治疗方案均显示出更高的 irAE 风险。
结论
nab-PTX/PTX+ICIs 与 ICI 单药治疗相比，irAE 风险降低。这一发现支持 ICIs+nab-PTX/PTX 可能是一种更安全的治疗策略。此外，我们还发现，含有 ICI 的联合方案比标准化疗具有更高的 irAE 风险。此外，与 ICIs+PTX 相比，ICIs+nab-PTX 降低了 irAE 的风险。PD-1 抑制剂与 irAE 风险高于 PD-L1 抑制剂相关。
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