FDA Approves Cabozantinib for Renal Cell Carcinoma

Toni Choueiri, MD

The FDA has approved cabozantinib (Cabometyx) as a treatment for patients with advanced renal cell carcinoma (RCC) who have received prior antiangiogenic therapy.

The approval was based on findings from the 658-patient phase III METEOR trial, in which the multikinase inhibitor cabozantinib demonstrated a 42% reduction in the risk of progression or death compared with everolimus (Afinitor) 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).

Cabozantinib also reduced the risk of death by 34% in the intent-to-treat population. Median overall survival was 21.4 months for patients receiving cabozantinib versus 16.5 months for those receiving everolimus (HR, 0.66; 95% CI 0.53-0.83; P = .0003).

“The efficacy profile demonstrated by Cabometyx in the METEOR trial, now complemented by the overall survival benefit, is highly compelling,” Toni Choueiri, MD, clinical director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, said in a statement.

“Cabometyx is distinct from other approved treatment options, as it targets multiple tyrosine kinases involved in the development of RCC, including MET, AXL, and 3 VEGF receptors. At the same time, physicians are very familiar with this class of drug and how to use dose adjustments to balance safety and efficacy. The approval of Cabometyx is wonderful news for physicians who are looking for a new option for their previously treated patients with advanced kidney cancer.”

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 ≥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 confirmed response rate, as reported by the FDA in a statement, was 17% (95% CI, 13-22) in the cabozantinib arm versus 3% (95% CI, 2-6) in the everolimus arm.

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.

“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,” Michael M. Morrissey, PhD, president and chief executive officer of Exelixis, the manufacturer of cabozantinib, said in a statement. “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.

The FDA initially approved cabozantinib in November 2012 as a treatment for patients with metastatic medullary thyroid cancer.

Choueiri TK, Escudier B, Powles T, et al. Cabozantinib versus everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015;373(19):1814-1823.