FDA Grants Priority Review to Frontline Cabozantinib in RCC

Gisela Schwab, MD

The FDA has granted a priority review to a supplemental new drug application (sNDA) for cabozantinib (Cabometyx) for previously untreated patients with advanced renal cell carcinoma (RCC), according to Exelixis, the developer of the multikinase inhibitor.

The sNDA is based on the phase II CABOSUN trial, in which cabozantinib reduced the risk of progression or death by 34% versus sunitinib (Sutent) as a first-line treatment for patients with metastatic RCC. The median progression-free survival was 2.6 months longer with cabozantinib versus sunitinib, at 8.2 versus 5.6 months (HR, 0.66; 95% CI, 0.46-0.95; P = .012).

Under the Prescription Drug User Fee Act the FDA is scheduled to make its decision on the sNDA by February 15, 2018.

“The acceptance of the sNDA filing with a priority review is an important regulatory milestone for Cabometyx and for our mission to improve treatment outcomes for patients with cancer,” Gisela Schwab, MD, president, Product Development and Medical Affairs and chief medical officer, Exelixis, said in a statement. “We look forward to working with the FDA as they review the application in our effort to offer Cabometyx to patients with previously untreated metastatic RCC who are in need of new treatment options.”

In the CABOSUN trial, researchers randomly assigned patients to 60 mg daily of cabozantinib (n = 79) or 50 mg daily of sunitinib (n = 78) for 4 weeks on followed by 2 weeks off. Eligible patients were required to have locally advanced or metastatic clear-cell RCC, ECOG performance status 0 to 2, and had to be intermediate or poor risk per the IMDC criteria. Prior systemic treatment for RCC was not permitted.

Median age across the entire patient population was 63 years (range, 31-87), 78% of patients were male, and 92% were white. Thirty-six percent of patients had bone metastases and 75% of patients had prior nephrectomy. Patients had an ECOG performance status of 0 (45.9%), 1 (41.4%), or 2 (12.7%).

Median overall survival was 30.3 months in the cabozantinib arm versus 21.8 months in the sunitinib arm (HR, 0.80; 95% CI, 0.50-1.26). Cabozantinib was also superior for overall response rate, at 46% versus 18%.

In 87% of the cabozantinib arm, there was some reduction in target lesions, compared with 44% of the sunitinib cohort. The stable and progressive disease rates were 33% versus 36% and 18% versus 26%, respectively.

Adverse events (AEs) of any grade occurred in approximately 99% of each arm. The most common all-grade AEs with cabozantinib versus sunitinib included fatigue (85.9% vs 81.9%), hypertension (80.8% vs 68.1%), diarrhea (71.8% vs 52.8%), increased AST (61.5% vs 31.9%), and increased ALT (55.1% vs 27.8%).

Grade ≥3 AEs occurred in 66.7% of the cabozantinib arm versus 68.1% of the sunitinib arm. Common grade ≥3 AEs included diarrhea (10.3% with cabozantinib vs 11.1% with sunitinib), fatigue (6% vs 15%), hypertension (28.2% vs 22.2%), palmar-plantar erythrodysesthesia (7.7% vs 4.2%), and fatigue (6.4% vs 15.3%).

Patients in the cabozantinib arm were more likely to require dose reductions, 58% versus 49%. There were 16 AE-related discontinuations in each arm.

Cabozantinib is approved by the FDA as a treatment for patients with advanced RCC who have received prior antiangiogenic therapy.

Choueiri TK, Halabi S, Sanford BL, et al. Cabozantinib versus sunitinib as initial targeted therapy for patients with metastatic renal cell carcinoma of poor or intermediate risk: the alliance A031203 CABOSUN trial. J Clin Oncol. 2017;35(6):591-597. doi:10.1200/JCO.2016.70.7398.