Endocrine adverse events in patients with cancer receiving perioperative immune checkpoint blockade: a meta-analysis of randomized controlled trials

Abstract

Background: Perioperative use of immune checkpoint blockade (ICB) improves survival in patients with early-stage cancer. Treatment-related adverse events (AEs), frequently involve the endocrine system which may increase perioperative complications and affect quality of life. Objective: We conducted a meta-analysis to elucidate the impact of adding ICB to conventional neoadjuvant/adjuvant therapy on the incidence of endocrine AEs. Design: A systematic review and meta-analysis of randomize-controlled trials (RCTs). Data sources and methods: A systematic search of PubMed, Embase, Web of Science, and Cochrane library was performed for RCTs comparing groups with and without the addition of ICB to conventional perioperative therapy in patients with cancer. Outcomes included all-grade and grade 3–5 thyroiditis, hyperthyroidism, hypothyroidism, adrenal insufficiency, hypophysitis, type 1 diabetes mellitus, and hyperglycemia. The odds ratios (ORs) of all-grade and grade 3–5 endocrine were pooled using the random-effect model meta-analysis. Results: Twenty-four RCTs comprising 12,199 patients were identified for meta-analysis. The addition of ICB was associated with higher incidence of thyroiditis [all grade: OR = 3.53 (95% confidence interval (CI): 1.88–6.64)], hyperthyroidism [all-grade: 7.18 (4.30–12.01); grade 3–5: 3.93 (1.21–12.82)], hypothyroidism [all-grade: 5.39 (3.68–7.90); grade 3–5: 3.63 (1.18–11.11)], adrenal insufficiency [all-grade: 3.82 (1.88–7.79); grade 3–5: 5.91 (2.36–14.82)], hypophysitis [all-grade: 10.29 (4.97–21.3); grade 3–5: 5.80 (1.99–16.92)], and type 1 diabetes mellitus [all-grade: 2.24 (1.06–4.74); grade 3–5: 3.49 (1.21–10.08)]. The cumulative incidence of each grade 3–5 endocrine AE was low (<1.3%). No grade 5 AEs leading to death were observed. Conclusion: The addition of neoadjuvant/adjuvant ICB to conventional therapy was associated with an increased incidence of several endocrine AEs. Clinicians should be aware of the risk of endocrinopathy from the perioperative ICB use to facilitate risk–benefit discussion with patients with early-stage cancer. Trial registration: The protocol of this research was registered in PROSPERO (CRD42022332624).