On April 25, 2016, the U. S. Food and Drug Administration (FDA) approved cabozantinib (CABOMETYX{trade mark, serif}, Exelixis, Inc.) for the treatment of advanced renal cell carcinoma (RCC) in patients who have received prior anti-angiogenic therapy. The approval was based on data from one randomized, open-label, multicenter study in which RCC patients who had received prior anti-angiogenic 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 (IRC) 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 [HR 0.58 (95% 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 also was demonstrated, with 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.
Clinical cancer research : an official journal of the American Association for Cancer Research. 2016 Oct 28 [Epub ahead of print]
Harpreet Singh, Michael Brave, Julia A Beaver, Joyce Cheng, Shenghui Tang, Eias Zahalka, Todd R Palmby, Rajesh Venugopal, Pengfei Song, Qi Liu, Chao Liu, Jingyu Yu, Xiao Hong Chen, Xing Wang, Yaning Wang, Paul G Kluetz, Selena R Daniels, Elektra J Papadopoulos, Rajeshwari Sridhara, Amy E McKee, Amna Ibrahim, Geoffrey Kim, Richard Pazdur
Office of Hematology Oncology Products (OHOP), Division of Oncology Products 1 (DOP1), U.S. Food and Drug Administration, Center for Drug Evaluation and Research (CDER) ., Division of Drug Oncology Products, US Food and Drug Administration., Center for Drug Evaluation and Research, U.S. Food and Drug Administration., Office of Clinical Pharmacology, FDA., CDER, FDA., OFfice of Hematology and Oncology Products, US Food and Drug Administration., Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, US Food and Drug Administration., OHOP, U.S. Food and Drug Administration, Center for Drug Evaluation and Research (CDER)., Office of Hematology and Oncology Products, Food And Drug Administration., Office of Clinical Pharmacology, Food & Drug Administration., Clinical Pharmacology, U.S. Food and Drug Administration, Center for Drug Evaluation and Research (CDER)., Office of Translational Sciences, U.S. Food and Drug Administration., Office of New Drugs Quality Assurance, FDA., Office of New Drug Products, U.S. Food and Drug Administration, Center for Drug Evaluation and Research (CDER)., Office of Clinical Pharmacology, Division of Pharmacometrics, FDA., Office of Hematology and Oncology Products, Food and Drug Administration., Office of Oncology Drug Products, U.S. Food and Drug Administration., Clinical Outcomes Assessment Staff, Food and Drug Administration., Office of Biostatistics, FDA., Medical Oncology Branch, National Cancer Institute.