Acquired hypothyroidism as a predictive marker of outcome in patients with metastatic renal cell carcinoma (mRCC) treated with tyrosine-kinase inhibitors (TKIs): A literature-based meta-analysis.

Abstract

500 Background: The development of hypothyroidism in patients with mRCC during treatment with the tyrosine kinase inhibitors (TKIs) sunitinib and sorafenib is a well-established side effect. The potential role of hypothyroidism as predictive marker of outcome has been studied with conflicting results. The aim of the present meta-analysis was to assess the predictive value of hypothyroidism for both progression free (PFS) and overall survival (OS) in patients with mRCC treated with TKI. Methods: We searched PubMed as well as the electronic abstract databases of the major international congresses’ proceedings to identify all eligible studies which reported a correlation of the development of hypothyroidism during treatment with TKI and outcome in patients with mRCC. Hazard ratios (HRs) with 95% confidence intervals (CIs) for PFS and OS were obtained from these publications and pooled in a meta-analysis by using random-effects or fixed-effects models based on the heterogeneity of the included studies. Results: Eleven studies with a total of 500 patients fulfilled the inclusion criteria. We found no statistical significant difference in PFS between patients who developed hypothyroidism and patients without hypothyroidism during sunitinib therapy (HR: 0.82, 95% CI: 0.59-1.13, p-value = 0.22) (6 studies; 250 patients). For studies that included patients treated with either sunitinib or sorafenib, the development of hypothyroidism was found to be predictive for longer progression free survival (HR: 0.59, 95% CI: 0.42-0.84, p-value = 0.003) (3 studies; 205 patients). The HR for OS was 0.52 (95% CI: 0.31-0.87, p-value = 0.01) for patients who developed hypothyroidism during sunitinib therapy compared to patients without hypothyroidism (4 studies; 147 patients). Conclusions: The development of hypothyroidism during TKIs therapy is not clearly shown to be predictive in patients with mRCC. The observed advantage in overall survival for patients with treatment related hypothyroidism should be interpreted with caution due to the potential imbalance of treatments received after first line treatment in each group.