1. Safety and Efficacy of PD-1/PD-L1 inhibitors combined with radiotherapy in patients with non-small-cell lung cancer: a systematic review and meta-analysis
- Author
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Yichao Geng, Zheng Li, Xueshan Zhao, Lina Wang, Qiuning Zhang, Xiaohu Wang, Shuangwu Feng, Chengcheng Li, Ruifeng Liu, Zhen Yang, Hongtao Luo, and Bing Lu
- Subjects
0301 basic medicine ,Oncology ,combined radio‐immunotherapy ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Combination therapy ,medicine.medical_treatment ,Programmed Cell Death 1 Receptor ,Radiosurgery ,lcsh:RC254-282 ,B7-H1 Antigen ,03 medical and health sciences ,0302 clinical medicine ,systematic review ,Internal medicine ,Carcinoma, Non-Small-Cell Lung ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Lung cancer ,Adverse effect ,Immune Checkpoint Inhibitors ,non‐small‐cell lung cancer ,radiotherapy ,Pneumonitis ,Randomized Controlled Trials as Topic ,Original Research ,business.industry ,Clinical Cancer Research ,Odds ratio ,Chemoradiotherapy ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Combined Modality Therapy ,programmed cell death protein‐1/programmed cell death ligand‐1 inhibitors ,Clinical trial ,Radiation therapy ,Survival Rate ,030104 developmental biology ,meta‐analysis ,030220 oncology & carcinogenesis ,Immunotherapy ,business - Abstract
Background 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. Methods 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. Results 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. Conclusion 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., Radiotherapy combined with PD‐1/PD‐L1 inhibitors in the treatment of advanced NSCLC showed clinical long‐term survival benefit and short‐term efficacy benefit, and might not increase the serious adverse events.
- Published
- 2020