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

Background We 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. Methods An 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. Results A 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). Conclusions Both 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. [ABSTRACT FROM AUTHOR]