Evaluation safety and efficacy of immune checkpoint blockers (ICB) and radiotherapy combination versus ICB in non‐small cell lung cancer patients with recurrence or metastasis: A systematic review and meta‐analysis

BACKGROUND: 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. METHODS: 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. RESULTS: 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 (2)) = 0.00%, odds ratio (OR) 1.28, 95% confidence interval (CI) 1.09–1.49, I (2) = 0.00%, OR 1.12, 95% CI 1.00–1.25, I (2) = 42.1%, OR 0.81, 95% CI 0.72–0.92, I (2) = 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 (2) = 0.00%, OR 1.05, 95% CI 0.91–1.22, I (2) = 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). CONCLUSION: 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.