PURPOSE
Everolimus decreases tumor volume of renal angiomyolipomas in patients with tuberous sclerosis. No prospective data are available regarding the effect of everolimus on the growth kinetics in patients with sporadic angiomyolipomas. We sought to determine the safety and efficacy of everolimus in the volumetric reduction of sporadic angiomyolipomas.
MATERIALS AND METHODS
This multi-institutional, prospective, phase II trial, enrolled patients with ≥3cm sporadic angiomyolipomas who were candidates for surgical resection or percutaneous angioembolization. Patients received 10mg everolimus daily for four planed 28-day cycles. Response was defined as a ≥25% volumetric reduction of a patient's angiomyolipoma. Baseline, 4, 6 and 12-month volumetric analyses were performed using MRI. Everolimus was discontinued in those with <25% volumetric reduction after four cycles. Those with ≥ 25% volumetric reduction received two additional cycles. The primary outcomes were the efficacy of everolimus in the volumetric reduction of angiomyolipomas by ≥25% and the safety and tolerability of everolimus.
RESULTS
20 patients were enrolled at 5 centers. 11/20 (55%) patients completed 4 cycles, and 7/20 (35%) completed 6 cycles. Efficacy was demonstrated, with 10/18 (55.6%) patients exhibiting a ≥ 25% reduction in tumor volume at 4 months (median 58.5%) and 10/14 (71.4%) patients exhibiting a ≥25% reduction in tumor volume at 6 months (median 58.2%). 4/20 (20%) patients were withdrawn due to protocol-defined toxicities. 8/20 (40%) self-withdrew from the study due to side-effects.
CONCLUSIONS
Everolimus was effective in causing volumetric reduction of angiomyolipomas by ≥25% in most patients but was associated with a high rate of treatment discontinuation.
TRIAL REGISTRATION
ClinicalTrials.gov: NCT02539459.Trial Sponsor:Novartis Pharmaceuticals Corporation.