The FDA has granted a priority review designation to cabozantinib as a treatment for patients with advanced renal cell carcinoma following progression on one prior therapy.
The FDA has granted a priority review designation to cabozantinib (Cometriq) as a treatment for patients with advanced renal cell carcinoma (RCC) following progression on one prior therapy, according to a statement from the drug's developer, Exelixis.
The application for cabozantinib was based on findings from the 658-patient phase III METEOR trial, in which cabozantinib demonstrated a 42% reduction in the risk of progression or death compared with everolimus in patients with advanced RCC. After a minimum of 11 months of follow-up, median progression-free survival (PFS) with cabozantinib was 7.4 months compared with 3.8 months with everolimus (HR, 0.58; 95% CI, 0.45-0.75; P <.001).
Data for the application were submitted on a rolling basis as part of a breakthrough therapy designation that was received by the multikinase inhibitor in August 2015. Under the Prescription Drug User Fee Act, the FDA is scheduled to make a ruling on the application by June 22, 2016; however, Exelixis is preparing for an earlier decision.
“With FDA granting Priority Review to our application, Exelixis is one step closer to offering physicians cabozantinib as an important new therapeutic option for their patients with advanced renal cell carcinoma,” Michael M. Morrissey, PhD, president and CEO of Exelixis, said in a statement. “While we work closely with the FDA during the review process, Exelixis will continue to execute on our commercial plans, including our commitment to be ready for a potential launch by April first of this year.”
In the METEOR study, 658 patients were randomized in a 1:1 ratio to receive daily cabozantinib at 60 mg (n = 330) or everolimus at 10 mg (n = 328). The primary endpoint of PFS was assessed on the first 375 patients enrolled in the trial. In this portion of the study, 187 patients were randomized to cabozantinib and 188 received everolimus.
The median age of patients was approximately 62 years (range, 31-86) and a majority had received one prior VEGFR TKI (71%), with approximately 29% of patients having received â‰¥2 prior therapies. Previous systemic therapy primarily consisted of sunitinib (62%), pazopanib (43%), and axitinib (16%). By MSK criteria, 46% of patients were in the favorable prognostic risk category, 41% were intermediate, and 13% were poor.
By investigator assessment, the median PFS was 7.4 months with cabozantinib and 5.3 months with everolimus (HR, 0.60; 95% CI, 0.47-0.76; P <.001). Cabozantinib was superior to everolimus for PFS across all subgroups. For those treated with only 1 prior therapy, there was a 44% reduction in the risk of progression or death with cabozantinib versus everolimus (HR, 0.56; 95% CI, 0.42-0.75).
The median duration of treatment with cabozantinib was 7.6 versus 4.4 months with everolimus. The objective response rate was 21% in those treated with cabozantinib versus 5% with everolimus (P <.001).
At the interim analysis for the full study population, a trend toward improvement in overall survival was observed; however, this did not pass a high bar for statistical significance (HR, 0.67; 95% CI, 0.51-0.89; P = .005). A P value of â‰¤.0019 was required to achieve significance. The survival follow-up will continue until the data mature.
Grade 3/4 AEs occurred in 68% of patients treated with cabozantinib versus 58% in those who received everolimus. The most common grade 3/4 AEs with cabozantinib were hypertension (15%), diarrhea (11%), and fatigue (9%) versus anemia (16%), fatigue (7%), and hyperglycemia (5%) with everolimus. Grade 5 AEs occurred in 7% of patients treated with cabozantinib and in 8% of those who received everolimus.
The most common serious AEs in the cabozantinib arm were abdominal pain (3%), pleural effusion (3%), and diarrhea (2%). In the everolimus group, the most common serious AEs were anemia (4%), dyspnea (4%), and pneumonia (4%). Dose reductions were required for 60% and 25% of patients, in the cabozantinib and everolimus arms, respectively. The discontinuation rate due to adverse events (AEs) was 9% in the cabozantinib arm versus 10% with everolimus.
In Europe, Exelixis completed a Marketing Authorization Application on January 11, 2016, for cabozantinib in RCC. The Committee for Medicinal Products for Human Use has granted an accelerated assessment to cabozantinib. Under this program, the agency will review the application in 150 days instead of the standard 210-days.
The FDA initially approved cabozantinib in November 2012 as a treatment for patients with metastatic medullary thyroid cancer. Further trials continue to explore agent in a number of solid tumors, including the phase III CELESTIAL trial, which is comparing cabozantinib to placebo for patients with HCC following treatment with sorafenib (NCT01908426).