March 2016, Vol. 5, No. 2

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Cabozantinib Improves Standard of Care for Second-Line Treatment of Advanced Kidney Cancer

Bernard Escudier, MD

Genitourinary Cancers Symposium

Bernard-Escudier98pxCabozantinib achieved superior progression-free survival (PFS) versus standard treatment with everolimus in patients with previously treated advanced kidney cancer in an updated analysis of the phase 3 METEOR trial reported at the Genitourinary Cancers Symposium. In addition, a strong trend toward overall survival (OS) favored cabozantinib at an interim analysis, showing a 33% improvement versus everolimus.

Final OS results will be presented at ASCO in June.

“Current treatments can provide some benefit to patients with advanced kidney cancer, but we need treatments that are more effective and can overcome treatment resistance. Our preliminary results suggest that cabozantinib may help overcome treatment resistance and provide new hope to patients with this aggressive cancer,” said lead author Bernard Escudier, MD, Institut Gustave Roussy, Villejuif, France.

Cabozantinib targets MET and AXL, which are associated with poor prognosis and resistance to tyrosine kinase inhibitors (TKIs), he noted.

The study enrolled 658 patients with advanced kidney cancer previously treated with 1 or 2 lines of therapy (vascular endothelial growth factor receptor TKI or checkpoint inhibitor therapy). Brain metastases were allowed if treated and controlled. Patients were randomized to receive either cabozantinib 60 mg orally every day or everolimus 10 mg orally every day and were treated until loss of benefit or intolerable toxicity.

PFS was reported in the first 375 patients enrolled in the trial at an interim analysis and was 7.4 months with cabozantinib versus 3.9 months with everolimus (P <.001), representing a 48% reduction in risk of disease progression favoring cabozantinib.

Cabozantinib led to improved PFS versus everolimus across all subtypes, regardless of risk category, metastatic sites, and number and type of prior treatments.

In an exploratory analysis of PFS, cabozantinib appeared to be even more effective in patients with bone metastasis, patients who previously took sunitinib, and those in whom prior checkpoint inhibitor therapy had failed.

PFS was especially impressive with cabozantinib in patients who previously received sunitinib: median PFS was 9.1 months in the cabozantinib group. “This has never been seen before,” Escudier said.

Only 32 patients had prior checkpoint inhibitor therapy, so improved PFS in this small subgroup is hypothesis-generating and needs further study.

Side effects commonly reported with cabozantinib included diarrhea, fatigue, nausea and vomiting, and hand-foot syndrome. Common side effects reported with everolimus included fatigue, anemia, decreased appetite, cough, and dyspnea.

Many patients are now getting nivolumab, a checkpoint inhibitor, as second-line therapy, Escudier said.

“These findings exceed what we have seen before in this setting. Virtually all patients derive benefit from cabozantinib, even the most challenging patients, for example, those with bone metastases,” said Sumanta Pal, MD, moderator of a press conference where this research was featured. Pal is Assistant Clinical Professor, Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA, and an ASCO spokesperson.

“Cabozantinib has a compelling benefit in tumor growth and a hint of survival benefit. I would tend to favor cabozantinib over nivolumab as a second-line option,” Pal said.

Escudier said that the numbers in this study are too small to base a second-line choice on. “I would be cautious in interpreting this. The hazard ratio was impressive, but this is a small group of patients.”

Escudier predicted that cabozantinib will become the drug of choice after failure of programmed death-1 or its ligand 1.

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