As reported by Toni K. Choueiri, MD, of Dana-Farber Cancer Institute, et al in The Lancet Oncology, the final results of the phase III METEOR trial indicate significantly improved overall survival with cabozantinib (Cabometyx) vs everolimus (Afinitor) in patients with advanced renal cell carcinoma that had progressed after previous vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor treatment. Cabozantinib inhibits tyrosine kinases including MET, VEGFR, and AXL.
A previous report from the open-label phase III METEOR trial showed that progression-free survival, the primary endpoint, was significantly prolonged with cabozantinib vs everolimus in the first 375 randomized patients (median, 7.4 vs 3.8 months; hazard ratio [HR] = 0.58; P < .001), as assessed by independent radiology review committee.
Overall, 658 patients were randomly assigned between August 2013 and November 2014 to receive cabozantinib (n = 330) or everolimus (n = 328). The median duration of follow-up was 18.7 months in the cabozantinib group and 18.8 months in the everolimus group.
Objective response rates were 17% with cabozantinib vs 3% with everolimus (P < .0001). Median overall survival was 21.4 months in the cabozantinib group vs 16.5 months in the everolimus group (HR = 0.66, P = .00026). Median progression-free survival was 7.4 months vs 3.9 months (HR = 0.51, P < .0001), consistent with the earlier report from the trial. Systemic anticancer treatment was used in 50% of the cabozantinib group and 55% of the everolimus group after discontinuation of the study treatment.
The most common grade 3 or 4 adverse events in the cabozantinib group were hypertension (15% vs 4%), diarrhea (13% vs 2%), fatigue (11% vs 7%), palmar-plantar erythrodysesthesia syndrome (8% vs 1%), anemia (6% vs 17%), and hypomagnesemia (5% vs 0%). Serious adverse events of grade ≥ 3 occurred in 39% vs 40% of patients.
Dose reductions were required in 62% vs 25% of patients, and treatment was discontinued due to adverse events in 12% vs 11%. Treatment-related deaths occurred in one patient in the cabozantinib group and two patients in the everolimus group.
The investigators concluded:
Treatment with cabozantinib increased overall survival, delayed disease progression, and improved the objective response compared with everolimus. Based on these results, cabozantinib should be considered as a new standard-of-care treatment option for previously treated patients with advanced renal cell carcinoma. Patients should be monitored for adverse events that might require dose modifications.
The study was funded by Exelixis Inc. ■