Department of Radiation Oncology, Beijing Chao-Yang Hospital Capital Medical University, Beijing, China.
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
BMJ Open. 2023 Mar 17;13(3):e059457. doi: 10.1136/bmjopen-2021-059457.
Based on the acknowledged organ-specific immune microenvironment, little is known regarding the efficacy of immunotherapy in patients with lung cancer according to metastatic sites. This meta-analysis aimed to explore the efficacy of immune checkpoint inhibitors (ICIs) vs chemotherapy in patients with lung cancer with liver metastases (LM) or brain metastases (BM).
Meta-analysis and systematic review.
We systematically searched in electronic databases (PubMed, EMBASE, Cochrane Library and Web of Science), up to 31 January 2022. We also reviewed the abstracts from major international conferences. Eligibility criteria were randomised controlled phase II or III trials reporting the overall survival (OS) or progression-free survival (PFS) of LM or BM subsets.
Hazard ratios (HRs) with 95% CIs for OS and PFS were extracted and aggregated using a random-effects model.
Twenty-four randomised controlled trials with available outcomes for patients with BMs or LMs were identified. A total of 1124 patients with BM and 2077 patients with LM were included in the analysis. The pooled OS HR of patients with LMs was 0.83 (95% CI 0.72 to 0.95), and that of patients without LM 0.73 (95% CI 0.69 to 0.79). LM was associated with less benefits from ICIs. In patients with BM treated with ICIs, the pooled OS HR compared with the control arms was 0.71 (95% CI 0.53 to 0.94). Subgroup analyses by histology suggested that only patients with non-small cell lung cancer (NSCLC) with BM could gain benefit from ICIs (HR 0.53, 95% CI 0.41 to 0.68). BM negatively influenced efficacy of immunotherapy in patients with small cell lung cancer.
Our results showed immunotherapy demonstrated efficacy in patients with lung cancer with LM and BM, survival benefits dominantly favoured patients with NSCLC. Patients with lung cancer with LM obtained less benefits from ICIs than those without. Therefore, organ-specific immunotherapeutic approaches should be considered.
CRD42020212797.
基于公认的器官特异性免疫微环境，对于转移性肺癌患者，根据转移部位，免疫疗法的疗效知之甚少。本荟萃分析旨在探讨免疫检查点抑制剂（ICI）与化疗在肺癌伴肝转移（LM）或脑转移（BM）患者中的疗效。
荟萃分析和系统评价。
我们系统地检索了电子数据库（PubMed、EMBASE、Cochrane 图书馆和 Web of Science），检索时间截至 2022 年 1 月 31 日。我们还查阅了主要国际会议的摘要。纳入标准为报告 LM 或 BM 亚组总生存期（OS）或无进展生存期（PFS）的随机对照 II 期或 III 期试验。
使用随机效应模型提取并汇总 OS 和 PFS 的风险比（HR）及其 95%置信区间。
共确定了 24 项有 BM 或 LM 结局的随机对照试验。共纳入 1124 例 BM 患者和 2077 例 LM 患者进行分析。LM 患者的 OS HR 为 0.83（95%CI 0.72 至 0.95），无 LM 患者的 OS HR 为 0.73（95%CI 0.69 至 0.79）。LM 与 ICI 获益减少相关。在接受 ICI 治疗的 BM 患者中，与对照组相比，OS HR 为 0.71（95%CI 0.53 至 0.94）。按组织学进行的亚组分析表明，只有 BM 非小细胞肺癌（NSCLC）患者可从 ICI 中获益（HR 0.53，95%CI 0.41 至 0.68）。BM 对小细胞肺癌患者免疫治疗的疗效有负面影响。
我们的结果表明，免疫疗法在肺癌伴 LM 和 BM 的患者中有效，生存获益主要有利于 NSCLC 患者。与无 LM 的患者相比，LM 患者从 ICI 中获益较少。因此，应考虑针对特定器官的免疫治疗方法。
PROSPERO 注册号：CRD42020212797。
