Cabozantinib (Cabometyx) achieved superior progression-free survival (PFS) versus standard treatment with everolimus in patients with previously treated advanced renal-cell carcinoma in an updated analysis of the phase 3 METEOR trial, the results of which were reported at the 2016 Genitourinary Cancers Symposium. In addition, a strong trend toward overall survival (OS) favored cabozantinib at an interim analysis, showing a 33% improvement versus everolimus. The final OS results will be presented at the 2016 American Society of Clinical Oncology (ASCO) annual meeting 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 investigator Bernard J. Escudier, MD, Chair, Genitourinary Oncology Committee, Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France. Cabozantinib targets the MET and AXL tyrosine kinases, which are associated with poor prognosis and resistance to tyrosine kinase inhibitors (TKIs), Dr Escudier noted. The study enrolled 658 patients with advanced kidney cancer who previously received 1 or 2 lines of therapy (ie, a vascular endothelial growth factor receptor TKI therapy). Patients with brain metastases were allowed in the trial if the metastases were treated and controlled. The patients were randomized to receive oral cabozantinib 60 mg or oral everolimus 10 mg daily, and they were treated until loss of benefit or intolerable toxicity. PFS was reported in the first 375 patients who were enrolled in the trial at an interim analysis. The median PFS was 7.4 months with cabozantinib versus 3.9 months with everolimus (P <.001), representing a 48% reduction in the risk for disease progression favoring cabozantinib. Cabozantinib led to improved PFS versus everolimus across all subtypes, regardless of risk category, metastatic site, and number and type of previous 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 in those whose disease did not progress with previous checkpoint inhibitor therapy. PFS was especially impressive with cabozantinib in patients who previously received sunitinib: the median PFS was 9.1 months in the cabozantinib group. “This has never been seen before,” Dr Escudier said. Only 32 patients received previous checkpoint inhibitor therapy, so improved PFS in this small subgroup is hypothesis-generating and needs further study. The side effects that were previously reported with cabozantinib included diarrhea, fatigue, nausea and vomiting, and hand-foot syndrome. The common side effects reported with everolimus included fatigue, anemia, decreased appetite, cough, and dyspnea. Many patients are now receiving nivolumab, a checkpoint inhibitor, as second-line therapy, Dr 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 K. Pal, MD, Co-director, Kidney Cancer Program, City of Hope, Duarte, CA, and ASCO spokesperson and moderator of a press conference where this research was featured. “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,” Dr Pal said. Dr Escudier said that the numbers in this study are too small to base a second-line choice of therapy on. “I would be cautious in interpreting this. The hazard ratio was impressive, but this is a small group of patients.” Dr Escudier predicted that cabozantinib will become the drug of choice after PD-1 or PD-1 ligand-1 failure. On April 25, 2016, the FDA approved cabozantinib (Cabometyx) for patients with advanced renal-cell carcinoma (see Cabometyx Receives FDA Approval for Advanced Renal-Cell Carcinoma).