Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Division of Neurosurgery, Department of Surgery, Queen's University, Kingston, Ontario, Canada.
World Neurosurg. 2022 Feb;158:e87-e102. doi: 10.1016/j.wneu.2021.10.113. Epub 2021 Oct 21.
As many as 30% of patients with non-small cell lung cancer (NSCLC) will develop brain metastases (BMs) over the course of their illness. Here, we quantitatively compare the efficacy of the various emerging regimens for NSCLC BMs without a definitive targetable epidermal growth factor receptor mutation/ALK rearrangement.
We searched MEDLINE, EMBASE, Web of Science, ClinicalTrials.gov, CENTRAL, and references of key studies for randomized controlled trials (RCTs) published from inception until June 2020. Comparative RCTs that included ≥10 patients were included. We used a frequentist fixed or random-effects model for network meta-analysis. The outcomes of interest included intracranial progression-free survival (iPFS), overall survival (OS), and overall progression-free survival.
In total, 18 studies representing 17 trials (n = 2726 patients) were identified. Immune checkpoint inhibitor regimens showed significant improvement in OS compared with chemotherapy alone, including pembrolizumab and chemotherapy (6 studies, hazard ratio [HR] 0.36, 95% confidence interval [CI] 0.21-0.62), atezolizumab alone (HR 0.54, 95% CI 0.33-0.89), and nivolumab and ipilimumab (HR 0.64, 95% CI 0.42-0.97). An improvement in overall PFS was seen with use of pembrolizumab and chemotherapy compared with chemotherapy alone (3 studies, HR 0.42, 95% CI 0.26-0.68). Studies evaluating checkpoint inhibitors did not report iPFS data, and we did not find improvement in iPFS or OS with the addition of any chemotherapy regimen to whole-brain radiation therapy.
In this network meta-analysis, we demonstrate the promising survival benefit with use of checkpoint inhibitor-based regimens in NSCLC BMs without a targetable epidermal growth factor receptor mutation/ALK rearrangement. Moving forward, large-scale BM-focused RCTs are necessary to establish the iPFS benefit of immune checkpoint inhibitor-based immunotherapy in this patient population.
多达 30%的非小细胞肺癌（NSCLC）患者在疾病过程中会发展为脑转移（BMs）。在这里，我们定量比较了各种新兴方案治疗无明确可靶向表皮生长因子受体突变/ALK 重排的 NSCLC BMs 的疗效。
我们检索了 MEDLINE、EMBASE、Web of Science、ClinicalTrials.gov、CENTRAL 以及关键研究的参考文献，以获取自成立以来至 2020 年 6 月发表的随机对照试验（RCT）。纳入了纳入≥10 例患者的比较性 RCT。我们使用固定或随机效应模型进行网络荟萃分析。感兴趣的结局包括颅内无进展生存期（iPFS）、总生存期（OS）和总体无进展生存期。
共确定了 18 项研究，代表了 17 项试验（n=2726 例患者）。与单独化疗相比，免疫检查点抑制剂方案在 OS 方面显示出显著改善，包括 pembrolizumab 联合化疗（6 项研究，风险比 [HR] 0.36，95%置信区间 [CI] 0.21-0.62）、atezolizumab 单药（HR 0.54，95% CI 0.33-0.89）和 nivolumab 联合 ipilimumab（HR 0.64，95% CI 0.42-0.97）。与单独化疗相比，pembrolizumab 联合化疗可改善总体 PFS（3 项研究，HR 0.42，95% CI 0.26-0.68）。评估检查点抑制剂的研究未报告 iPFS 数据，我们也未发现添加任何化疗方案联合全脑放疗可改善 iPFS 或 OS。
在这项网络荟萃分析中，我们证明了在无明确可靶向表皮生长因子受体突变/ALK 重排的 NSCLC BMs 中使用基于检查点抑制剂的方案具有有希望的生存获益。未来，需要进行大规模的以 BM 为重点的 RCT，以确定免疫检查点抑制剂为基础的免疫疗法在该患者人群中的 iPFS 获益。
