Incidence of Endocrine Dysfunction Following the Use of Different Immune Checkpoint Inhibitor Regimens: A Systematic Review and Meta-analysis

摘要: Importance If not promptly recognized, endocrine dysfunction can be life threatening. The incidence and risk of developing such adverse events (AEs) following the use immune checkpoint inhibitor (ICI) regimens are unknown. Objective To compare AEs treatment with US Food Drug Administration–approved ICI regimens. Data Sources A PubMed search through July 18, 2016, using keywords was performed: “ipilimumab,” “MDX-010,” “nivolumab,” “BMS-963558,” “pembrolizumab,” “MK-3475,” “atezolizumab,” “MPDL3280A,” “phase.” Study Selection Thirty-eight randomized clinical trials evaluating usage these ICIs for advanced solid tumors were identified, resulting in a total 7551 patients who eligible meta-analysis. Regimens categorized by class into monotherapy PD-1 (programmed cell death protein 1) inhibitor, CTLA-4 (cytotoxic T-lymphocyte-associated protein-4) or PD-L1 1 ligand combination therapy plus inhibitors. Extraction Synthesis data extracted primary reviewer (R.B.-S.) then independently reviewed 2 secondary reviewers (W.T.B. A.C.G.-C.) Preferred Reporting Items Systematic Reviews Meta-analyses guidelines. Inferences on made log-odds random effects models. Main Outcomes Measures Incidence all-grade hypothyroidism, hyperthyroidism, hypophysitis, adrenal insufficiency, insulin-deficient diabetes. Results Overall, 38 comprising included this systematic review both hypothyroidism hyperthyroidism highest receiving therapy. Patients regimen significantly more likely to experience (odds ratio [OR], 3.81; 95% CI, 2.10-6.91, P  = .001) than ipilimumab. Compared ipilimumab, those inhibitors had higher (OR, 1.89; 1.17-3.05;  = .03). but greater 5.36; 2.04-14.08;  = .002). While received less hypophysitis ipilimumab 0.29; 0.18-0.49;  = .001). For insufficiency diabetes no statistical inferences due smaller number events. Conclusions Relevance Our study provides precise dysfunctions among at increased thyroid hypophysitis.