SUN-LB043 Phase 2 Randomized Study of the Efficacy and Safety of Testosterone in Metastatic Renal Cell Carcinoma Patients with Hypogonadism

Introduction: Metastatic renal cell carcinoma (mRCC) can cause hypogonadism as an adverse effect in male patients. Hypogonadism can also result from adverse effects of targeted therapy of mRCC, such as fatigue, pain, anorexia, asthenia or hypothyroidism. The objective of this multicenter randomized phase 2 study was to determine efficacy and safety of testosterone undecanoate (T) in mRCC patients with hypogonadism. Methods: Eighty-two male patients with clear cell mRCC were screened. Patients with low testosterone level and normal PSA level receiving first-line sunitinib or pazopanib were randomly assigned (1:1) to either T (Nebido®, 1,000 mg) and targeted therapy or targeted therapy alone (control group). T was injected intramuscular deeply on Day 1 of a new treatment cycle. Symptom index (FKSI-19), fatigue score (FACIT-Fatigue), erectile function (IIEF-5), testosterone serum concentrations, red blood cells (RBC) count and hemoglobin level were evaluated. The assessments were performed at baseline and Day 28 of a treatment cycle. Results: Sixty (75.6%) patients had hypogonadism. Mean age was 52 years (range 33-71) in the T group (N=30) and 55 years (42-69) in the control group (N=30). 45 (75%) patients reported a negative change in their sexual life, and 16 (27%) patients had no sexual activity since the start of the targeted therapy. T was well tolerated in mRCC patients. No unexpected toxicity was observed. The health-related quality-of-life scores in the T group were better than those in the control group, respectively (mean (SD) - FKSI-19: baseline, 46.5 (12.2) vs. 44.2 (9.4), Day 28, 27.5 (12.5) vs. 39.9 (9.8); FACIT-Fatigue: baseline, 37 (4.7) vs. 35.3 (3.1), Day 28, 20.3 (8.1) vs. 42.5 (8.4), all P≤0.01). Therapy with T improved significantly sexual function (IIEF-5: baseline, 16 (3.3) vs. 19 (2.6), Day 28, 21 (1.5) vs. 8 (1.9), P=0.003). There was non-significant positive trend in hemoglobin level between 2 groups (baseline, 124.5 (11.7) g/l vs. 119 (10.4), Day 28, 133 (13.5) vs. 108 (17). Testosterone level increased significantly in T group (baseline, 6.21 (1.78) nmol/l, Day 28, 33.2 (14.3). Conclusions: Male patients with mRCC receiving targeted therapy had significantly less fatigue, better symptom control, and better erectile function with T. T therapy was safe. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.