Medical College of Yangzhou University, Yangzhou, China.
Northern Jiangsu People's Hospital, Yangzhou, China.
Cancer Med. 2023 Jul;12(13):13928-13941. doi: 10.1002/cam4.5958. Epub 2023 Jun 16.
Currently, immune checkpoint blockers (ICB) and radiotherapy (RT) combination therapy is broadly applied in non-small cell lung cancer (NSCLC) patients. However, meta-analysis about safety and efficacy of RT + ICB versus ICB has not yet been reported. To evaluate safety and efficacy of the combination therapy of ICB and RT in patients with recurrent or metastatic NSCLC and explore factors related to higher response rates, longer lifetime, and lower toxicity, meta-analysis of previous clinical data will be presented in this article.
A literature search on patients with recurrent or metastatic NSCLC treated with RT + ICB versus ICB was performed using the Cochrane Library, Embase and PubMed up to December 10, 2022. Suitable quality assessment checklists were selected corresponding to various types of research studies. Comparative and single-arm studies were analyzed using Stata 14.0.
10 comparative studies and 15 arms of combination therapy were included for this meta-analysis. RT significantly improved objective response rate (ORR), disease control rate (DCR), and overall survival (OS) and progression-free survival (PFS) of ICB (I-square value (I ) = 0.00%, odds ratio (OR) 1.28, 95% confidence interval (CI) 1.09-1.49, I = 0.00%, OR 1.12, 95% CI 1.00-1.25, I = 42.1%, OR 0.81, 95% CI 0.72-0.92, I = 34.5%, OR 0.80, and 95% CI 0.71-0.89, respectively). Toxicity between combination therapy and ICB monotherapy did not significantly differ in any grade or in ≥3 grade of tr-AEs (I = 0.00%, OR 1.05, 95% CI 0.91-1.22, I = 0.00%, OR 1.46, 95% CI 0.90-2.37, respectively). Subgroup analyses based on single-arm studies showed that applications of SRS/SBRT, PD-1 inhibitor, and administration of ICB after RT were conducive to a better DCR, longer OS and mild adverse events (heterogeneity between groups (HBG) all p < 0.05).
RT can significantly improve ORR, DCR, OS, and PFS of ICB in patients with recurrent or metastatic NSCLC without increasing toxicity. PD-1 inhibitor following SRS/SBRT could be the best option to maximally benefit the patients.
目前，免疫检查点抑制剂（ICB）联合放疗（RT）在非小细胞肺癌（NSCLC）患者中广泛应用。然而，尚未有关于 RT+ICB 与 ICB 疗效和安全性的荟萃分析。为了评估 ICB 联合 RT 治疗复发性或转移性 NSCLC 患者的安全性和疗效，并探讨与更高缓解率、更长生存期和更低毒性相关的因素，本文将对先前的临床数据进行荟萃分析。
检索 Cochrane 图书馆、Embase 和 PubMed 数据库，检索时间截至 2022 年 12 月 10 日，对接受 RT+ICB 与 ICB 治疗的复发性或转移性 NSCLC 患者进行文献检索。根据不同类型的研究选择合适的质量评估检查表。采用 Stata 14.0 对比较性和单臂研究进行分析。
本荟萃分析纳入了 10 项比较研究和 15 个联合治疗臂。RT 显著提高了 ICB 的客观缓解率（ORR）、疾病控制率（DCR）、总生存期（OS）和无进展生存期（PFS）（I 平方值（I ）=0.00%，优势比（OR）1.28，95%置信区间（CI）1.09-1.49，I =0.00%，OR 1.12，95% CI 1.00-1.25，I =42.1%，OR 0.81，95% CI 0.72-0.92，I =34.5%，OR 0.80，95% CI 0.71-0.89）。联合治疗与 ICB 单药治疗的任何级别或≥3 级 TRAE 毒性无显著差异（I =0.00%，OR 1.05，95% CI 0.91-1.22，I =0.00%，OR 1.46，95% CI 0.90-2.37）。基于单臂研究的亚组分析表明，SRS/SBRT、PD-1 抑制剂的应用和 RT 后 ICB 的应用有利于更好的 DCR、更长的 OS 和较轻的不良反应（组间异质性（HBG）均 p<0.05）。
RT 可显著提高复发性或转移性 NSCLC 患者 ICB 的 ORR、DCR、OS 和 PFS，而不增加毒性。SRS/SBRT 后使用 PD-1 抑制剂可能是使患者最大获益的最佳选择。
