The First School of Clinical Medicine, Lanzhou University, Lanzhou, China.
Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China.
Cancer Med. 2021 Feb;10(4):1222-1239. doi: 10.1002/cam4.3718. Epub 2021 Jan 19.
A combination of programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) inhibitors and radiotherapy (RT) is increasingly being used to treat non-small-cell lung cancer (NSCLC). However, the safety and efficacy of this approach remains controversial. We performed a systematic review and meta-analysis to summarize the related research.
We searched the China Biology Medicine, EMBASE, Cochrane Library, and PubMed databases for all the relevant studies. The Stata software, version 12.0 was used for the meta-analysis.
The study included 20 clinical trials that enrolled 2027 patients with NSCLC. Compared with non-combination therapy, combination therapy using PD-1/PD-L1 inhibitors and RT was associated with prolonged overall survival (OS) (1-year OS: odds ratio [OR] 1.77, 95% confidence interval [CI] 1.35-2.33, p = 0.000; 2-year OS: OR 1.77, 95% CI 1.35-2.33, p = 0.000) and progression-free survival (PFS) (0.5-year PFS: OR 1.83, 95% CI 1.13-2.98, p = 0.014; 1-year PFS: OR 2.09, 95% CI 1.29-3.38, p = 0.003; 2-year PFS: OR 2.47, 95% CI 1.13-5.37, p = 0.023). Combination therapy also improved the objective response rate (OR 2.76, 95% CI 1.06-7.19, p = 0.038) and disease control rate (OR 1.80, 95% CI 1.21-2.68, p = 0.004). This meta-analysis showed that compared with non-combination therapy, combination therapy using PD-1/PD-L1 inhibitors and RT did not increase the serious adverse event rates (≥grade 3); however, this approach increased the rate of grade 1-2 immune-related or radiation pneumonitis. Subgroup analyses revealed that the sequence of PD-1/PD-L1 inhibitors followed RT outperformed in which concurrent PD-1/PD-L1 inhibitor and RT followed PD-1/PD-L1 inhibitor. Combination of stereotactic body RT or stereotactic radiosurgery with PD-1/PD-L1 inhibitors may be more effective than a combination of conventional RT with PD-1/PD-L1 inhibitors in patients with advanced NSCLC.
Combination therapy using PD-1/PD-L1 inhibitors and RT may improve OS, PFS, and tumor response rates without an increase in serious adverse events in patients with advanced NSCLC. However, combination therapy was shown to increase the incidence of mild pneumonitis.
程序性细胞死亡蛋白-1（PD-1）/程序性细胞死亡配体-1（PD-L1）抑制剂与放射治疗（RT）联合应用于治疗非小细胞肺癌（NSCLC）的情况越来越多。然而，这种方法的安全性和疗效仍存在争议。我们进行了系统回顾和荟萃分析，以总结相关研究。
我们检索了中国生物医学文献数据库、EMBASE、Cochrane 图书馆和 PubMed 数据库，以获取所有相关研究。采用 Stata 软件（版本 12.0）进行荟萃分析。
本研究纳入了 20 项临床试验，共纳入 2027 例 NSCLC 患者。与非联合治疗相比，PD-1/PD-L1 抑制剂联合 RT 的联合治疗可延长总生存期（OS）（1 年 OS：比值比 [OR] 1.77，95%置信区间 [CI] 1.35-2.33，p=0.000；2 年 OS：OR 1.77，95%CI 1.35-2.33，p=0.000）和无进展生存期（PFS）（0.5 年 PFS：OR 1.83，95%CI 1.13-2.98，p=0.014；1 年 PFS：OR 2.09，95%CI 1.29-3.38，p=0.003；2 年 PFS：OR 2.47，95%CI 1.13-5.37，p=0.023）。联合治疗还可提高客观缓解率（OR 2.76，95%CI 1.06-7.19，p=0.038）和疾病控制率（OR 1.80，95%CI 1.21-2.68，p=0.004）。本荟萃分析表明，与非联合治疗相比，PD-1/PD-L1 抑制剂联合 RT 的联合治疗并未增加严重不良事件发生率（≥3 级）；然而，这种方法增加了 1-2 级免疫相关或放射性肺炎的发生率。亚组分析显示，PD-1/PD-L1 抑制剂序贯 RT 的疗效优于 PD-1/PD-L1 抑制剂同步 RT。立体定向体部 RT 或立体定向放射外科与 PD-1/PD-L1 抑制剂联合应用可能比常规 RT 与 PD-1/PD-L1 抑制剂联合应用在晚期 NSCLC 患者中更有效。
PD-1/PD-L1 抑制剂与 RT 联合治疗可改善晚期 NSCLC 患者的 OS、PFS 和肿瘤缓解率，而不会增加严重不良事件。然而，联合治疗显示出增加轻度肺炎的发生率。
