Risk of hypothyroidism in patients with cancer treated with sunitinib: A systematic review and meta-analysis

Background. The multitargeted tyrosine kinase inhibitor sunitinib is used in various cancers. Clinical studies have reported a substantial variation in the incidence of hypothyroidism associated with sunitinib, without a systemic attempt to synthesize these data. Methods. We searched Medline databases for relevant clinical trials published up to May 2012. Phase II and III trials and expanded access programs of sunitinib in patients with any type of cancer that reported occurrence of hypothyroidism were eligible. The summary incidence, relative risk (RR) and 95% confidence intervals (CIs) were calculated using random- or fixed-effects models based on the heterogeneity of included studies. Results. Incidence analysis was performed using 6678 sunitinib-treated patients from all 24 eligible trials. The incidence of all-and high-grade hypothyroidism was 9.8% (95% CI 7.3-12.4%) and 0.4% (95% CI 0.3-0.5%), respectively. A meta-analysis of seven randomized trials with 2787 subjects revealed a RR of all- and high-grade hypothyroidism of 13.95 (95% CI 6.91-28.15; p<0.00001) and 4.78 (95% CI 1.09-20.84; p=0.04), respectively. Subgroup analysis revealed a significantly higher incidence of all-grade hypothyroidism in patients receiving sunitinib for longer duration than in patients receiving sunitinib for shorter duration (p=0.02). Conclusions. This meta-analysis of data available from clinical trials demonstrates that sunitinib is associated with a significant risk of developing all- and high-grade hypothyroidism. These data provide further evidence to recommend monitoring for hypothyroidism in patients receiving sunitinib.