FDA Approves Cabozantinib for Advanced Renal Cell Carcinoma

Patients diagnosed with advanced renal cell carcinoma (RCC), who have received prior treatment with anti-angiogenic agents, now have the option of being treated with cabozantinib (Cabometyx), following its FDA approval.

A small molecule inhibitor that binds c-Met and VEGFR2, cabozantinib was granted orphan drug designation in 2011. The first approval for the drug was a year later, for the treatment of a rare form of thyroid cancer, but the drug failed to improve outcomes in patients with prostate cancer.

Today’s approval follows the results of the phase 3 METEOR trial that met its primary endpoint of progression-free survival (PFS) in 330 patients diagnosed with advanced RCC. The randomized controlled trial compared cabozantinib with the standard of care therapy, everolimus, which is currently used as second-line for RCC. Cabozantinib treatment resulted in a 42% reduction in the rate of disease progression or death compared with everolimus. Further, a significant advantage in PFS was observed with cabozantinib (7.4 months) compared with everolimus (3.8 months) (HR, 0.58; 95% CI 0.45-0.74, P<.0001).

Most importantly, and significant to today’s approval, was recent data that proved a survival advantage of cabozantinib: median overall survival in the intent-to-treat population was 21.4 months, compared with 16.5 months for patients treated with everolimus (HR, 0.66; 95% CI, 0.53-0.83; P = .0003).

“With today’s announcement, patients with previously treated advanced kidney cancer now have a new option, the first and only approved product demonstrated to help patients live longer while also delaying the progression of their cancer,” said Michael M. Morrissey, PhD, president and CEO of Exelixis, the company that has developed cabozantinib, in a press release. “We are proud to bring new hope to this community, who are looking for more therapies that can help extend lives. Exelixis is committed to making Cabometyx available to patients in need within the next couple weeks.”

Most common adverse events (AEs) associated with the drug include diarrhea, fatigue, nausea, decreased appetite, palmar-plantar erythrodysesthesia syndrome, hypertension, vomiting, weight decreased, and constipation. Serious AEs were reported in 40% of patients, the most common being abdominal pain, pleural effusion, diarrhea, and nausea.