期刊
BMC CANCER
卷 19, 期 -, 页码 -出版社
BMC
DOI: 10.1186/s12885-019-5701-6
关键词
Non-small cell lung cancer; Oncology; Programmed cell death protein-1; Programmed cell death ligand 1; Inhibitor; Immune-related adverse event; Meta-analysis; Systematic review
类别
资金
- National Key Research and Development Program of China [2018YFC1705301]
- National Natural Science Foundation of China [81874470, 81603627]
- Shanghai Rising-Star program [16QA1403800]
- Development Fund for Shanghai Talents [2017047]
- Young Talent Supporting Program of China Association of Traditional Chinese Medicine [QNRC2-B05]
- Hundred Talents Program of Shaanxi [SXBR9053]
- Shanghai Development Office of TCM [ZY (2018-2020)-FWTX-1008, ZY (2018-2020)-CCCX-2004-08, ZY (2018-2020)-FWTX-4010]
- Shanghai Shen Kang Hospital Development Center Project [16CR2035B]
- Budget project of Shanghai University of Traditional Chinese Medicine [18LK049]
BackgroundProgrammed cell death protein-1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors have remarkable clinical efficacy in the treatment of non-small cell lung cancer (NSCLC); however, the breakdown of immune escape causes a variety of immune-related adverse events (irAEs). With the increasing use of PD-1/PD-L1 inhibitors alone or in combination with other therapies, awareness and management of irAEs have become more important. We aimed to assess the incidence and nature of irAEs associated with PD-1 and PD-L1 inhibitors for NSCLC.MethodsArticles from the MEDLINE, EMBASE, and Cochrane databases were searched through December 2017. The incidence of overall and organ-specific irAEs was investigated in all clinical trials with nivolumab, pembrolizumab, atezolimumab, durvalumab, and avelumab as single agents for treatment of NSCLC. We calculated the pooled incidence using R software with package Meta.ResultsSixteen trials were included in the meta-analysis: 10 trials with PD-1 inhibitors (3734 patients) and 6 trials with PD-L1 inhibitors (2474 patients). The overall incidence of irAEs was 22% (95% confidence interval [CI], 17-28) for all grades and 4% (95% CI, 2-6) for high-grade irAEs. The frequency of irAEs varied based on drug type and organ, and patients treated with PD-1 inhibitors had an increased rate of any grade and high-grade irAEs compared with patients who received PD-L1 inhibitors. Organ-specific irAEs were most frequently observed in, in decreasing order, the endocrine system, skin, pulmonary tract, and gastrointestinal tract. The total number of patients whose death was attributed to irAEs was 14 (0.34%), and most (79%) of these patients died because of pneumonitis. The median time to the onset of irAEs after the initiation of treatment was 10weeks (interquartile range, 6-19.5weeks) and varied depending on the organ system involved.ConclusionsThe specificity of irAEs was closely associated with the mechanism of PD-1/PD-L1 antibodies involved in restarting anticancer immune attacks. Comprehensive understanding, timely detection, and effective management could improve the compliance of patients and guide the interruption of treatment.
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