Cabometyx Wins Indication for Previously Untreated Advanced Kidney Cancer

Approval granted well in advance of predicted PDUFA date

The FDA has approved a new indication for cabozantinib tablets (Cabometyx, Exelixis, Inc.) for treatment of patients with advanced renal cell carcinoma (RCC), the most common form of kidney cancer in adults.

The FDA’s priority review and approval were based on results from the randomized phase 2 CABOSUN trial in patients with previously untreated RCC, which demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) versus sunitinib (Sutent, Pfizer), a current standard of care. The FDA initially approved cabozantinib in April 2016 for the treatment of patients with advanced RCC who have previously received antiangiogenic therapy.

“The CABOSUN trial enrolled treatment-naïve patients with advanced kidney cancer, including those who are known to fare poorly, such as patients with intermediate- or poor-prognostic factors and those with bone metastases or multiple sites of metastatic disease,” said Toni Choueiri, MD, Director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute. “Physicians are already experienced in using Cabometyx in the second-line advanced RCC setting, and it is a much-needed advance to also now have Cabometyx as an option for their patients with previously untreated advanced RCC.”

The CABOSUN trial met its primary endpoint of improving PFS. According to the independent radiology review committee analysis of the data, cabozantinib demonstrated a clinically meaningful and statistically significant 52% reduction in the rate of disease progression or death (hazard ratio, 0.48; 95% confidence interval, 0.31–0.74, two-sided P = 0.0008). Median PFS for cabozantinib was 8.6 months versus 5.3 months for sunitinib, corresponding to a 3.3 month (62%) improvement.

All causality grade 3 or 4 adverse reactions occurred in 68% of patients receiving cabozantinib and 65% of patients receiving sunitinib. The most frequent all causality grade 3-4 adverse reactions (at least 5%) in patients treated with cabozantinib were hypertension, diarrhea, hyponatremia, hypophosphatemia, palmar-plantar erythrodysesthesia, fatigue, increased ALT, decreased appetite, stomatitis, pain, hypotension, and syncope. Twenty-one percent of patients in the cabozantinib arm compared to 22% of patients receiving sunitinib discontinued treatment due to adverse events.

CABOSUN was a randomized, open-label, active-controlled phase 2 trial that enrolled 157 patients with advanced RCC determined to be intermediate- or poor-risk by the IMDC criteria. Patients were randomized 1:1 to receive cabozantinib (60 mg once daily) or sunitinib (50 mg once daily, four weeks on followed by two weeks off). The primary endpoint was PFS. Secondary endpoints included overall survival, objective response rate, and safety. Eligible patients were required to have locally advanced or metastatic clear-cell RCC, ECOG performance status 0-2, and had to be intermediate or poor risk per the IMDC criteria. Prior systemic treatment for RCC was not permitted.

Source: Exelixis Inc.; December 20, 2017.

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