On April 25, 2016, the FDA approved cabozantinib (Cabometyx; Exelixis) for the treatment of patients with advanced renal-cell carcinoma (RCC) who had received anti-angiogenic therapy. The FDA granted this approval under its fast track and priority review procedures.
The approval was based on 1 randomized clinical trial of patients with advanced RCC who had previously received anti-angiogenic therapy and were randomized to oral cabozantinib 60 mg daily (N = 330) or to everolimus 10 mg orally once daily (N = 328). The primary end point was progression-free survival (PFS) in the first 375 randomized patients.
The median PFS in this group was 7.4 months with cabozantinib and 3.8 months with everolimus (P <.001). The median overall survival in the full study population was 21.4 and 16.5 months, respectively. The response rate was 17% versus 3%, respectively.
The safety of cabozantinib was evaluated in 331 patients. The most common adverse reactions included diarrhea, fatigue, nausea, decreased appetite, palmar-plantar erythrodysesthesia syndrome, hypertension, vomiting, weight loss, and constipation. In addition, 60% of patients receiving cabozantinib had ≥1dose reduction. Serious adverse events were reported in 40% of patients; these included abdominal pain, pleural effusion, diarrhea, and nausea. The recommended dose and schedule for cabozantinib is 60 mg orally daily.
Cabozantinib received a breakthrough therapy designation from the FDA in August 2015.