The tyrosine kinase inhibitor (TKI) cabozantinib significantly delayed progression of disease compared with everolimus in patients with advanced clear cell renal cell carcinoma (RCC) with prior vascular endothelial growth factor receptor TKI treatment, according to the results of an interim analysis of the phase III METEOR trial presented at the 2015 European Cancer Congress in Vienna (abstract LBA 4). Early overall survival data appear promising as well.
“I am very excited about the outcome of the study since the results may change the standard of care in patients with advanced kidney cancer who have received prior standard therapy that targets the vascular endothelial growth factor receptor (VEGFR),” said Toni Choueiri, MD, clinical director of the Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, in a prepared statement.
The METEOR trial randomly assigned 658 patients to cabozantinib 60 mg once daily or everolimus 10 mg once daily. All patients enrolled in the trial must have progressed within 6 months of their prior VEGFR TKI treatment. The primary endpoint of the study was progression-free survival.
At the meeting, Choueiri presented data from the first 375 of these patients.
Patients assigned to cabozantinib lived almost twice as long without disease progression compared with patients assigned everolimus. The median progression-free survival was 7.4 months for patients assigned cabozantinib compared with 3.8 months for patients assigned everolimus (hazard ratio [HR], 0.58 [95% confidence interval (CI), 0.45–0.75]).
Early data from an interim analysis of overall survival showed that it was one-third better among patients assigned to cabozantinib compared with everolimus (HR, 0.67 [95% CI, 0.51–0.89]).
Among the most common serious adverse events for patients assigned cabozantinib were abdominal pain (3%), pleural effusion (2.7%), and diarrhea (2.1%); in patients assigned everolimus they were anemia (3.7%), dyspnea (3.7%), and pneumonia (3.7%). Treatment discontinuation due to adverse events was similar among the two treatment arms.
“The METEOR results are important from a clinical and scientific point of view,” Choueiri said. “Overcoming mechanisms of tumor escape or resistance to standard therapies is critical for improving long-term outcome for our patients with advanced kidney cancer.”
According to Choueiri, additional studies of cabozantinib underway include a phase II study comparing the drug with sunitinib as a first treatment for advanced RCC and combination studies pairing cabozantinib with other emerging therapies, such as agents that boost the immune system.