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

Abstract

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 (I2) = 0.00%, odds ratio (OR) 1.28, 95% confidence interval (CI) 1.09–1.49, I2 = 0.00%, OR 1.12, 95% CI 1.00–1.25, I2 = 42.1%, OR 0.81, 95% CI 0.72–0.92, I2 = 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 (I2 = 0.00%, OR 1.05, 95% CI 0.91–1.22, I2 = 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.

Glutathione-Responsive and Hydrogen Sulfide Self-Generating Nanocages Based on Self-Weaving Technology To Optimize Cancer Immunotherapy

“…9,10 Currently, mono-ICB treatment benefits only less than 20% of cancer patients. 11 As early as in the 19th century, Rudolf Virchow pointed out the close connection between inflammation and the occurrence and development of tumors. 12 Recent studies further demonstrate that chronic inflammation is a facilitator of tumor progression and recurrence.…”

“…In recent years, immune checkpoint blockade (ICB) therapy, which seeks to reactivate the innate and adaptive immune systems to attack tumor cells, has been widely regarded as one of the promising antitumor recurrence strategies, , whether in combination with surgery or as monotherapy . Since the Food and Drug Administration (FDA) approved ipilimumab (anticytotoxic T lymphocyte antigen 4 antibody (anti-CTLA4)) as the ICB agent for the treatment of metastatic melanoma in 2011, multiple antibodies targeting the programmed cell death 1 (PD-1) and PD-1 ligand 1 (PD-L1) axis have also shown early success in cancer therapy. , However, individual differences in patients and the immunosuppressive tumor microenvironment (ITME) often result in unexpected inefficiencies of ICB therapy. , Currently, mono-ICB treatment benefits only less than 20% of cancer patients …”