The risk of immune-related endocrine disorders associated with anti-PD-1 inhibitors therapy for solid tumors: A systematic review and meta-analysis

Publication date: June 2018
Source:International Immunopharmacology, Volume 59
Author(s): Qiang Su, Xiao-chen Zhang, Di-ya Wang, Huai-rong Zhang, Cheng Zhu, Yan-li Hou, Jun-li Liu, Zu-hua Gao
BackgroundWe performed a systematic review and meta-analysis to evaluate the risk of immune-related endocrine disorders associated with PD-1 inhibitors therapy for solid tumors.MethodsAn Embase and PubMed search through December 6, 2017, using the following keywords was performed: immune-related endocrine disorders, and PD-1 inhibitors, etc. The data were analyzed using R 3.4.3 (R Project) and the metafor package. Patients treated with chemotherapy alone were used as control for the purpose of comparison.ResultsA total of 12 clinical trials including 5577 patients were found eligible for the meta-analysis. Compared with chemotherapy, the risk ratios of all-grade endocrine disorders are 13.89, (95% CI: 5.35–36.05, p < 0.001) for nivolumab therapy, and 9.85, (95% CI: 5.65–17.17, p < 0.001) for pembrolizumab therapy. The risk of all-grade hypothyroidism and hyperthyroidism incidence was increased for nivolumab therapy (hypothyroidism: RR 10.07, 95% CI: 3.37–30.11, p < 0.001; hyperthyroidism: RR 4.29, 95% CI: 1.13–16.30, p = 0.034) and for pembrolizumab therapy (hypothyroidism: RR 7.73, 95% CI: 3.86–15.49, p < 0.001; hyperthyroidism: RR 5.09, 95% CI: 2.36–10.97, p < 0.001). There was a significant increase in the risk of grade 1–5 endocrine disorders incidence for ipilimumab-nivolumab combination therapy (versus ipilimumab, RR 3.20, 95% CI: 2.08–4.91, p < 0.001; versus nivolumab, RR 2.54, 95% CI: 1.70–3.80, p < 0.001).ConclusionsBoth nivolumab and pembrolizumab therapy could result in a higher risk of all-grade immune-related endocrine disorders than chemotherapy. Nivolumab and ipilimumab combination therapy could result in an even higher risk of all-grade immune-related endocrine disorders than ipilimumab or nivolumab alone. Awareness of these side effects could guide clinicians to better manage the patients treated with anti-PD-1 inhibitors therapy for solid tumors.



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