Cabozantinib New Standard for Previously Treated Advanced RCC

June 20, 2016

Cabozantinib significantly improved the overall survival of patients with previously treated advanced RCC, according to the second interim analysis of the METEOR trial.

Cabozantinib, an oral tyrosine kinase inhibitor (TKI), significantly improved the overall survival of patients with previously treated advanced renal cell carcinoma (RCC), according to the second interim analysis results of the METEOR trial (abstract 4506), presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting, held earlier this month in Chicago.

Overall survival was a secondary endpoint of the METEOR trial. Initial results of the trial looking at the first 375 randomized patients showed significant improvement in progression-free survival (primary endpoint) for patients assigned cabozantinib compared with everolimus, but second interim analysis also showed a trend towards significant improvement in overall survival.

“In the METEOR phase III trial, treatment with cabozantinib was associated with a significant improvement in overall survival, as well as progression-free survival and objective response rate, compared with everolimus in advanced RCC,” said study presenter Toni K. Choueiri, MD, of Dana-Farber Cancer Institute in Boston. “Cabozantinib was recently approved by the FDA and is a new treatment standard for patients with RCC after antiangiogenic therapy.”

The trial enrolled a total of 658 patients with advanced RCC and randomly assigned them to cabozantinib 60 mg daily or everolimus 10 mg daily. All patients had treatment with at least one prior vascular endothelial growth factor (VEGF) receptor TKI, the most common being sunitinib and pazopanib.

Choueiri presented progression-free survival results looking at all 658 patients who were randomized to treatment. These results were similar to earlier results, with a median progression-free survival of 7.4 months for patients assigned cabozantinib compared with 3.9 months for those assigned everolimus (P < .0001). The objective response rate for patients treated with cabozantinib was 17% according to independent review and 24% according to investigator assessment.

Patients assigned cabozantinib had a 34% improvement in overall survival compared with everolimus (hazard ratio [HR], 0.66 [95% CI, 0.53–0.83]; P = .0003). The median overall survival was 21.4 months for cabozantinib compared with 16.5 months for everolimus.

Choueiri noted that an overall survival benefit associated with cabozantinib was consistently observed in all prespecified subgroups, including the Memorial Sloan Kettering Cancer Center prognostic risk group, the number of prior VEGF receptor TKIs, and the treatment duration of first VEGF receptor TKI, as well as location of organ metastasis.

In addition, the benefit of cabozantinib was seen in patients with both high and low MET expression status, indicating a benefit for the drug regardless of MET expression level.

The researchers also looked at the activity of cabozantinib in patients with bone metastases. Their analysis revealed that cabozantinib significantly improved overall survival in patients with bone metastases (HR, 0.54 [95% CI, 0.34–0.84]) and patients with bone and visceral metastases (HR, 0.45 [95% CI, 0.28–0.72]) compared with everolimus.

“We believe these results warrant further investigation into the underlying activity of cabozantinib in the bones,” Choueiri said.

Updated safety results showed a similar profile for cabozantinib to what was previously reported. The most common all-causality adverse events were diarrhea, fatigue, nausea, decreased appetite, hand-foot syndrome, hypertension, decreased weight, and vomiting.