The incidence of thyroid-related adverse events in solid tumors receiving immune checkpoint blockade with curative intent: A meta-analysis.

person Susu Zhou Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Beth Israel., New York, NY info_outline Susu Zhou, Nobuyuki Horita, Theresa Shao, Matthew Harrington, Yu Fujiwara

Authors person Susu Zhou Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Beth Israel., New York, NY info_outline Susu Zhou, Nobuyuki Horita, Theresa Shao, Matthew Harrington, Yu Fujiwara Organizations Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Beth Israel., New York, NY, Chemotherapy Center, Yokohama City University Hospital, Yokohama, Japan, Division of Hematology and Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai., New York, NY, Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Beth Israel, New York, NY Abstract Disclosures Research Funding No funding received None. Background: Adjuvant/neoadjuvant treatments with immune checkpoint blockade (ICB) improve survival outcomes in patients with several types of cancer. However, immune-related adverse events (irAEs) which frequently involve the thyroid gland may lead to delays in curative treatments such as surgery and radiotherapy. Thus, it is essential to report the incidence of thyroid-related adverse events (AEs) associated with the addition of ICB to conventional therapy with curative intent through a meta-analysis of randomized controls trials (RCTs). Methods: We performed a systematic search of PubMed, Embase, Web of Science, and Cochrane library for RCTs evaluating ICB-containing treatment of solid tumors with curative intent. We calculated the odds ratio (OR) of all-grade and grade 3-5 thyroid-related AEs including thyroiditis, hyperthyroidism, and hypothyroidism. We performed a meta-analysis using the random-effect model to compare the incidence of thyroid-related AEs in patients who received therapy with and without the addition of ICB. Subgroup analysis based on the type of ICB (anti-PD-1, anti-PD-L1, and anti-CTLA-4) was conducted. Results: 24 RCTs comprising 12,199 patients were analyzed. The addition of ICB was associated with higher incidence of all-grade thyroiditis (OR=3.53, 95%CI:1.88-6.64, p<0.0001), hyperthyroidism (OR=7.18, 95%CI:4.30-12.01, p<0.00001), and hypothyroidism (OR=5.39, 95%CI:3.68-7.90, p<0.00001). In subgroup analysis, PD-1 and PD-L1 inhibitors were particularly associated with higher incidence of hyperthyroidism and hypothyroidism. The incidence of grade 3-5 thyroid-related AEs in patients who received therapy with the addition of ICB was 0.13% (thyroiditis, N=4/3135), 0.20% (hyperthyroidism, N=12/5877), and 0.19% (hypothyroidism, N=12/6369). Conclusions: The addition of ICB to conventional therapy with curative intent was associated with an increased risk of all-grade thyroid-related AEs, but the incidence of grade 3-5 AEs was low. These results suggest ICB may be added safely as an adjunct to curative treatments such as surgery and radiotherapy. Clinicians should monitor patients’ thyroid function and maintain vigilance for symptoms and signs of thyroid disease. OR (95% CI) and number of studies (N) for thyroid-related AEs with subgroup analysis. All Anti-CTLA-4 Anti-PD-1 Anti-PD-L1 OR N OR N OR N OR N Thyroiditis All 3.53 (1.88-6.64) 8 9.87 (0.52-187.9) 1 3.23 (1.64-6.35) 5 5.13 (0.60-44.2) 2 G3-5 3.57 (0.42-30.6) 2 ― 0 3.57 (0.42-30.6) 2 ― 0 Hyperthyroidism All 7.18 (4.30-12.0) 22 1.99 (0.54-7.33) 4 11.2 (5.89-21.3) 10 6.25 (2.69-14.5) 8 G3-5 3.93 (1.21-12.8) 7 6.29 (0.70-56.7) 2 2.83 (0.46-17.4) 3 3.97 (0.44-36.0) 2 Hypothyroidism All 5.39 (3.68-7.90) 24 1.70 (0.51-5.68) 6 5.72 (4.21-7.77) 10 8.02 (3.11-20.7) 8 G3-5 3.63 (1.18-11.1) 7 3.03 (0.12-74.5) 1 4.30 (0.90-20.6) 4 3.03 (0.48-19.3) 2