U.S. Food and Drug Administration Approval: Cabozantinib for the Treatment of Advanced Renal Cell Carcinoma

• Published in: Clinical cancer research 2017-01, Vol.23 (2), p.330-335
• Main Authors: Singh, Harpreet, Brave, Michael, Beaver, Julia A, Cheng, Joyce, Tang, Shenghui, Zahalka, Eias, Palmby, Todd R, Venugopal, Rajesh, Song, Pengfei, Liu, Qi, Liu, Chao, Yu, Jingyu, Chen, Xiao Hong, Wang, Xing, Wang, Yaning, Kluetz, Paul G, Daniels, Selena R, Papadopoulos, Elektra J, Sridhara, Rajeshwari, McKee, Amy E, Ibrahim, Amna, Kim, Geoffrey, Pazdur, Richard
• Format: Article
• Language: English
• Subjects: Adult; Aged; Angiogenesis Inhibitors - administration & dosage; Angiogenesis Inhibitors - adverse effects; Anilides - administration & dosage; Anilides - adverse effects; Antiangiogenics; Appetite loss; Body weight loss; Carcinoma, Renal Cell - drug therapy; Carcinoma, Renal Cell - pathology; Confidence intervals; Constipation; Diarrhea; Disease-Free Survival; Drug Approval; Drug-Related Side Effects and Adverse Reactions - pathology; Fatigue; FDA approval; Female; Humans; Hypertension; Male; Middle Aged; Nausea; Patients; Protein Kinase Inhibitors - administration & dosage; Protein Kinase Inhibitors - adverse effects; Pyridines - administration & dosage; Pyridines - adverse effects; Radiology; Randomization; Regulatory agencies; Renal cell carcinoma; Statistical analysis; Statistical significance; Survival; Therapy; United States; United States Food and Drug Administration; Vomiting
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-16-1073

On April 25, 2016, the FDA approved cabozantinib (Cabometyx; Exelixis, Inc.) for the treatment of advanced renal cell carcinoma (RCC) in patients who have received prior antiangiogenic therapy. The approval was based on data from one randomized, open-label, multicenter study in which patients with RCC who had received prior antiangiogenic therapy were treated with either cabozantinib 60 mg orally once daily (n = 330) or everolimus 10 mg orally once daily (n = 328). The major efficacy outcome measure was progression-free survival (PFS) as assessed by a blinded independent radiology review committee in the first 375 randomized patients. A statistically significant improvement in PFS was seen, with a median PFS of 7.4 and 3.8 months in the cabozantinib and everolimus arms, respectively [hazard ratio (HR), 0.58; 95% confidence interval (CI), 0.45-0.74; P < 0.0001]. At a second interim analysis, a statistically significant improvement in overall survival (OS) in the intent-to-treat population was also demonstrated, with a median OS of 21.4 and 16.5 months in the cabozantinib and everolimus arms, respectively (HR, 0.66; 95% CI, 0.53-0.83; P = 0.0003). The most common (greater than or equal to 25%) adverse reactions included diarrhea, fatigue, nausea, decreased appetite, palmar-plantar erythrodysesthesia syndrome, hypertension, vomiting, weight loss, and constipation. Clin Cancer Res; 23(2); 330-5. ©2016 AACR.