Double‐blind, randomized, phase 2 trial of maintenance sunitinib versus placebo after response to chemotherapy in patients with advanced urothelial carcinoma

• Published in: Cancer 2014-03, Vol.120 (5), p.692-701
• Main Authors: Grivas, Petros D., Daignault, Stephanie, Tagawa, Scott T., Nanus, David M., Stadler, Walter M., Dreicer, Robert, Kohli, Manish, Petrylak, Daniel P., Vaughn, David J., Bylow, Kathryn A., Wong, Steven G., Sottnik, Joseph L., Keller, Evan T., Al‐Hawary, Mahmoud, Smith, David C., Hussain, Maha
• Format: Article
• Language: English
• Subjects: Adult; Aged; angiogenesis; Angiogenesis Inhibitors - administration & dosage; Angiogenesis Inhibitors - therapeutic use; Antineoplastic Agents - therapeutic use; Biological and medical sciences; bladder cancer; Carcinoma, Transitional Cell - drug therapy; chemotherapy; Confounding Factors (Epidemiology); Disease Progression; Disease-Free Survival; Double-Blind Method; Drug Administration Schedule; Early Termination of Clinical Trials; Female; Humans; Indoles - administration & dosage; Indoles - therapeutic use; Kaplan-Meier Estimate; maintenance therapy; Male; Medical sciences; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Nephrology. Urinary tract diseases; Pyrroles - administration & dosage; Pyrroles - therapeutic use; Sample Size; sunitinib; Treatment Outcome; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Urologic Neoplasms - drug therapy; urothelial carcinoma; Vascular Endothelial Growth Factor A - blood; Vascular Endothelial Growth Factor Receptor-2 - antagonists & inhibitors; Vascular Endothelial Growth Factor Receptor-2 - blood
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.28477

BACKGROUND Angiogenesis contributes to the progression of urothelial carcinoma (UC). In the current study, the authors investigated the role of maintenance sunitinib in patients with advanced UC. METHODS Patients with locally recurrent/metastatic UC and adequate organ function who achieved stable disease or a partial or complete response after 4 to 6 chemotherapy cycles were randomized to sunitinib at a dose of 50 mg/day (28 days on and 14 days off) or placebo. The primary endpoint was the 6‐month progression rate. Secondary endpoints were safety, survival, change in serum vascular endothelial growth factor (VEGF)/soluble VEGF receptor‐2 (sVEGFR2), and the activity of sunitinib in patients who developed disease progression while receiving placebo. A total of 38 eligible patients per treatment arm were required to select better therapy with 90% probability (α = .05). RESULTS A total of 54 eligible patients were randomized to either the sunitinib arm (26 patients) or the placebo arm (28 patients). The median number of cycles received was 2 cycles per treatment arm. The most common grade 3 to 4 adverse events (graded according to version 3.0 of the National Cancer Institute Common Terminology Criteria for Adverse Events) among patients receiving sunitinib were thrombocytopenia, diarrhea, mucositis, fatigue, and hypertension. There were no grade 3 or 4 adverse events noted among > 5% of patients receiving placebo. The 6‐month progression rate was 72% versus 64%. The median progression‐free survival (PFS) was 2.9 months (range, 0.5 months‐32.5 months) versus 2.7 months (range, 0.8 months −65 months) for the sunitinib versus placebo arms, respectively. Patients receiving placebo were found to have no changes in their serum VEGF/sVEGFR2 levels over time. Patients treated with sunitinib had no significant change in their VEGF level, but the sVEGFR2 level significantly decreased after cycles 1 and 2 (P