FDA Approves Cabometyx for Renal Cell Carcinoma

Patients with advanced renal cell carcinoma (RCC) who have received prior antiangiogenic therapy now have one more possible treatment option as the FDA approved Cabometyx (cabozantinib).

The approval was based on findings from the 658-patient phase 3 METEOR trial, in which the multikinase inhibitor Cabometyx demonstrated a 42 percent reduction in the risk of progression or death compared with Afinitor (everolimus) in patients with advanced RCC. After a minimum of 11 months of follow-up, median progression-free survival (PFS) with Cabometyx was 7.4 months compared with 3.8 months with Afinitor.

Cabometyx also reduced the risk of death by 34 percent in the intent-to-treat population. Median overall survival was 21.4 months for patients receiving Cabometyx versus 16.5 months for those receiving Afinitor.

“The efficacy profile demonstrated by Cabometyx in the METEOR trial, now complemented by the overall survival benefit, is highly compelling,” Toni Choueiri, 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 three 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 Cabometyx at 60 mg (330 patients) or Afinitor at 10 mg (328 patients). 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 Cabometyx and 188 received Afinitor.

The median age of patients was approximately 62 years (range, 31-86) and a majority had received one prior VEGFR TKI (71 percent), with approximately 29 percent of patients having received at least two prior therapies. Previous systemic therapy primarily consisted of Sutent (sunitinib) (62 percent), Votrient (pazopanib) (43 percent) and Inlyta (axitinib) (16 percent). By MSK criteria, 46 percent of patients were in the favorable prognostic risk category, 41 percent were intermediate, and 13 percent were poor.

By investigator assessment, the median PFS was 7.4 months with Cabometyx and 5.3 months with Afinitor. Cabometyx was superior to Afinitor for PFS across all subgroups. For those treated with only one prior therapy, there was a 44 percent reduction in the risk of progression or death with Cabometyx versus Afinitor.

The median duration of treatment with Cabometyx was 7.6 versus 4.4 months with Afinitor. The confirmed response rate, as reported by the FDA in a statement, was 17 percent in the Cabometyx arm verus 3 percent in the Afinitor arm.

Grade 3/4 AEs occurred in 68 percent of patients treated with Cabometyx versus 58 percent in those who received Afinitor. The most common grade 3/4 AEs with Cabometyx were hypertension (15 percent), diarrhea (11 percent) and fatigue (9 percent) versus anemia (16 percent), fatigue (7 percent) and hyperglycemia (5 percent) with Afinitor. Grade 5 AEs occurred in 7 percent of patients treated with Cabometyx and in 8 percent of those who received Afinitor.

The most common serious AEs in the Cabometyx arm were abdominal pain (3 percent), pleural effusion (3 percent), and diarrhea (2 percent). In the Afinitor group, the most common serious AEs were anemia (4 percent), dyspnea (4 percent), and pneumonia (4 percent). Dose reductions were required for 60 percent and 25 percent of patients, in the Cabometyx and Afinitor arms, respectively. The discontinuation rate due to adverse events (AEs) was 9 percent in the Cabometyx arm versus 10 percent with Afinitor.

“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, president and chief executive officer of Exelixis, the manufacturer of Cabometyx, 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 Cabometyx in November 2012 as a treatment for patients with metastatic medullary thyroid cancer.