Statistics Unit, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain; SOLTI Cancer Research Group, Barcelona, Spain.
Prostate Cancer Translational Research Group, VHIO, Barcelona, Spain; Oncology Data Science, VHIO, Barcelona, Spain.
Cancer Treat Rev. 2024 Dec;131:102847. doi: 10.1016/j.ctrv.2024.102847. Epub 2024 Oct 18.
Combining antibody-drug conjugate (ADCs) with immune checkpoint inhibitors (ICIs) is emerging as a promising treatment option to increase efficacy outcomes. However, concerns arise regarding the safety of these combinations, as some toxicities may overlap. Currently, there is still limited information about the safety profiles of this strategy.
A systematic review and meta-analysis was conducted to identify clinical trials investigating FDA-approved ADCs in combination with ICI drugs in the metastatic setting across all solid tumors. The primary endpoint of this study was the percentage of adverse events (AEs) of any grade and grade ≥ 3. Secondary endpoints include the percentage of patients with AEs leading to death, treatment discontinuation, proportion of complete responses (CR) and overall response rate (ORR). A parallel search was conducted to quantify the safety profile of ADCs and ICIs in monotherapy. Random effects models were used to estimate pooled outcomes.
Sixteen trials involving 1,133 patients treated with ADC plus ICI met the inclusion criteria with six different ADCs evaluated. Overall, 55.3 % of patients developed grade ≥ 3 AEs, 30.0 % of patients had treatment discontinuation, and 3.0 % experienced AEs leading to death. When compared to trials evaluating ADC or ICI as monotherapy, the combination results in similar rates of the most common AEs. However, it increases the risk of specific toxicities, such as ILD/pneumonitis (15.0 % with T-DXd plus ICI vs. 11.5 % with T-DXd alone). The pooled ORR was 48.8 % (95 %CI 39.4 % - 58.4 %) and the CR rate was 9.0 % (95 %CI 5.5 - 14.5). PD-L1-positive tumors showed numerically better efficacy outcomes.
This meta-analysis shows that the safety profile of the ADC plus ICI is comparable to that of ADC monotherapy. However, it increases the risk of certain toxicities of special interest, such as ILD/pneumonitis, highlighting the need for careful monitoring.
抗体药物偶联物（ADC）与免疫检查点抑制剂（ICI）联合使用，作为提高疗效的治疗方案正在兴起。然而，这些联合治疗的安全性令人担忧，因为一些毒性可能会重叠。目前，关于这种治疗策略的安全性概况信息仍然有限。
进行了系统评价和荟萃分析，以确定在所有实体瘤的转移性环境中，研究 FDA 批准的 ADC 与 ICI 药物联合应用的临床试验。本研究的主要终点是任何等级和等级≥3 的不良事件（AE）的百分比。次要终点包括因 AE 导致死亡、治疗中止、完全缓解（CR）和总缓解率（ORR）的患者比例。还进行了平行搜索以量化 ADC 和 ICI 单药治疗的安全性概况。使用随机效应模型估计汇总结果。
纳入了 1133 名接受 ADC 加 ICI 治疗的患者的 16 项试验，评估了六种不同的 ADC。总体而言，55.3%的患者发生了等级≥3 的 AE，30.0%的患者停止了治疗，3.0%的患者因 AE 导致死亡。与评估 ADC 或 ICI 单药治疗的试验相比，联合治疗导致最常见 AE 的发生率相似。然而，它增加了特定毒性的风险，例如间质性肺病/肺炎（T-DXd 加 ICI 为 15.0%，而 T-DXd 单药为 11.5%）。汇总 ORR 为 48.8%（95%CI 39.4% - 58.4%），CR 率为 9.0%（95%CI 5.5% - 14.5%）。PD-L1 阳性肿瘤显示出更好的疗效。
这项荟萃分析表明，ADC 加 ICI 的安全性与 ADC 单药治疗相当。然而，它增加了某些特殊关注毒性的风险，例如间质性肺病/肺炎，这强调了需要仔细监测。
