恶性肿瘤免疫治疗与性别的关系 | 引经据典[3]·协和呼吸
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肿瘤患者免疫治疗的疗效与其性别相关性的荟萃分析
Cancer immunotherapy efficacy and patients’sex:a systematic review and meta-analysis
小神药PD-1抗体类的
抗癌疗效与性别有关吗？
关键词
恶性肿瘤，免疫治疗，性别差异，荟萃分析
作者：Fabio Conforti, et al.
翻译: 北京协和医院呼吸内科 刘潇衍 黄慧
文献来源：Lancet Oncol. 2018 May 16.
pii: S1470-2045(18)30261-4
PMID:29778737
DOI:10.1016/S1470-2045(18)30261-4
背景及目的
尽管不同性别患者在免疫应答方面有所差异，但目前尚缺乏系统研究。该荟萃分析拟评价性别差异对于免疫检查点抑制剂抗肿瘤疗效的影响。
02
方 法
系统检索了PubMed，MEDLINE，Embase和Scopus数据库中从建库至2017年11月30日期间所有关于免疫检查点抑制剂（PD-1抑制剂, CTLA-4抑制剂，或二者联合）的随机对照研究，并且获取了这些研究根据性别分组的死亡风险比；此外，还回顾了大会摘要和报告（不包括非随机对照试验和非英文论文）。主要研究终点是男性和女性恶性肿瘤患者接受免疫检查点抑制剂的疗效差异，以总生存的死亡风险HR来衡量。
03
结 果
共检索得到7133项相关研究，符合上述条件的RCT研究20项（免疫检查点抑制剂包括ipilimumab，tremelimumab，nivolumab或pembrolizumab）。该荟萃分析共纳入11351例晚期或转移性肿瘤患者，其中男性7646例（67%），女性3705例（33%）；以黑色素瘤患者3632（32%）和非小细胞肺癌3482（31%）为主。与安慰剂组相比，接受免疫检查点抑制剂治疗的所有男性患者的总生存HR为0.72（95%CI 0.65-0.79），女性为0.86（95%CI：0.79-0.93）；两组之间存在显著性差异（p = 0.0019）。
04
结 论
免疫检查点抑制剂可延长晚期肿瘤（如黑色素瘤和非小细胞肺癌）患者的总生存期，但其获益程度与性别相关。将来可纳入更多女性患者，关注如何进一步改善女性患者免疫治疗的疗效，探索根据患者性别差异而采取不同的肿瘤免疫治疗方法。
原文摘要
Background
Despite the acknowledged sex-related dimorphism in immune system response, little is known about the effect of patients' sex on the efficacy of immune checkpoint inhibitors as cancer treatments. We did a systematic review and meta-analysis to assess the heterogeneity of immune checkpoint inhibitor efficacy between men and women.
Methods
We systematically searched PubMed, MEDLINE, Embase, and Scopus, from database inception to Nov 30, 2017, for randomised controlled trials of immune checkpoint inhibitors (inhibitors of PD-1, CTLA-4, or both) that had available hazard ratios (HRs) for death according to patients' sex. We also reviewed abstracts and presentations from all major conference proceedings. We excluded non-randomised trials and considered only papers published in English. The primary endpoint was to assess the difference in efficacy of immune checkpoint inhibitors between men and women, measured in terms of the difference in overall survival log(HR) reported in male and female study participants. We calculated the pooled overall survival HR and 95% CI in men and women using a random-effects model, and assessed the heterogeneity between the two estimates using an interaction test.
Findings
Of 7133 studies identified in our search, there were 20 eligible randomised controlled trials of immune checkpoint inhibitors (ipilimumab, tremelimumab, nivolumab, or pembrolizumab) that reported overall survival according to patients' sex. Overall, 11 351 patients with advanced or metastatic cancers (7646 [67%] men and 3705 [33%] women) were included in the analysis; the most common types of cancer were melanoma (3632 [32%]) and non-small-cell lung cancer (3482 [31%]). The pooled overall survival HR was 0·72 (95% CI 0·65–0·79) in male patients treated with immune checkpoint inhibitors, compared with men treated in control groups. In women treated with immune checkpoint inhibitors, the pooled overall survival HR compared with control groups was 0·86 (95% CI 0·79–0·93). The difference in efficacy between men and women treated with immune checkpoint inhibitors was significant (p=0·0019).
Interpretation
Immune checkpoint inhibitors can improve overall survival for patients with advanced cancers such as melanoma and non-small-cell lung cancer, but the magnitude of benefit is sex-dependent. Future research should guarantee greater inclusion of women in trials and focus on improving the effectiveness of immunotherapies in women, perhaps exploring different immunotherapeutic approaches in men and women.
作者介绍
刘潇衍
医学博士 北京协和医院内科临床博士后
博士期间主要从事呼吸系统恶性肿瘤内科治疗方面的临床和基础研究，在国内外期刊已发表论文10余篇。积极参与多个呼吸系统恶性肿瘤的国内外临床研究。
往期经典
文字来源：刘潇衍 黄慧
栏目负责：黄慧
版面编辑：陈珂琪
图片来源：部分来源于网络，如有侵权，请联系删除
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