A FARETES study of the efficacy and safety of testosterone in metastatic renal cell carcinoma patients with fatigue

Background: Fatigue is a frequent symptom of metastatic renal cell carcinoma (mRCC), and most common adverse event of treatment with tyrosine kinase inhibitors. The aim of this multicenter randomized phase 2 study was to determine efficacy and safety of testosterone undecanoate (T) in mRCC patients with fatigue developed during targeted therapy. Methods: Sixty male patients with clear cell mRCC, normal PSA level, low testosterone level and no evidence of hypothyroidism receiving first-line sunitinib or pazopanib with fatigue were randomly assigned (1:1) to either T and targeted therapy or targeted therapy alone (control group). T (1,000 mg) was injected intramuscular deeply on Day 1 of a new treatment cycle. The primary endpoint of the study was the difference in mean change of fatigue according to Functional Assessment of Cancer Therapy-Fatigue (FACIT-F). Secondary endpoints were safety, FKSI-19 score, testosterone serum concentrations, red blood cells (RBC) count and hemoglobin level. The assessments were performed at baseline and Day 28 of a treatment cycle. Results: T was well tolerated. No unexpected toxicity was observed. The health-related quality-of-life scores in the T group were better than those in the control group (Table). The current study did achieve its primary endpoint based on the significant differences favored T over targeted therapy alone regarding fatigue (all P≤0.012). Clinical trial information: NCT03379012. Conclusions: Male patients with mRCC receiving targeted therapy had significantly less fatigue and better symptom control with T. There was non-significant positive trend in hemoglobin level between 2 groups. T therapy was safe. Longterm outcomes will be reported. (Table Presented).