Cabozantinib Provides PFS Advantage in Advanced RCC

Patients with advanced renal cell carcinoma (RCC) treated with cabozantinib had improved progression-free survival (PFS) compared with those treated with the standard therapy, everolimus, according to results of the randomized METEOR phase III trial. The data were presented at a presscast ahead of the 2016 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium, held January 7–9 in San Francisco, by study author Bernard Escudier, MD, of the Institut Gustave Roussy in Villejuif, France (abstract 499).

The PFS benefit was seen in all patient subgroups, irrespective of prior treatment history, sites of metastasis, and risk category.

The METEOR study randomized 658 patients 1:1 to either 60 mg of cabozantinib daily or 10 mg of everolimus. All patients on trial were previously treated with at least one prior anti-VEGFR therapy. Using the Memorial Sloan Kettering Cancer Center risk assessment criteria, 43% of patients on study had favorable-risk disease, 41% had intermediate-risk disease, and 15% had poor-risk disease.

The initial results of the study, from the first 375 patients treated, showed a doubling of PFS for patients receiving cabozantinib compared with the control group, from 3.8 months in the everolimus arm to 7.4 months in the cabozantinib study arm.

The new update of the study included all 658 patients enrolled in the trial and showed that the PFS benefit from cabozantinib was maintained. The median PFS was 7.4 months in the cabozantinib arm compared with 3.9 months in the everolimus arm.

Among patients treated with cabozantinib, 75% had tumor shrinkage compared with 48% of patients in the everolimus treatment arm.

The most common side effects in patients receiving cabozantinib were diarrhea, fatigue, nausea, decreased appetite, and hand-foot syndrome. The most common side effects among patients receiving everolimus were fatigue, anemia, decreased appetite, cough, and dyspnea.

Cabozantinib is a small molecule, oral inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2) and c-Met. The drug is already approved for treatment of advanced medullary thyroid cancer and has a breakthrough therapy designation from the US Food and Drug Administration (FDA). In December, the drug’s manufacturer, Exelixis, submitted an application to extend the approval to renal cell carcinoma based on the results of the METEOR trial.

Cabozantinib appeared to be active following treatment with the anti–PD-1 immunotherapy nivolumab in the 30 patients who had been previously treated with this antibody, Escudier noted during his presentation.