The METEOR trial compared cabozantinib and everolimus in patients with advanced renal-cell carcinoma (RCC) that had progressed after VEGFR-targeted therapy. A total of 658 patients were randomly assigned to receive either cabozantinib (60 mg/day) or everolimus (10 mg/day). The primary endpoint was progression-free survival (PFS), with secondary endpoints including overall survival (OS) and objective response rate (ORR). Cabozantinib showed significantly longer PFS than everolimus, with median PFS of 7.4 months versus 3.8 months (hazard ratio 0.58, 95% CI 0.45–0.75, P<0.001). The ORR was 21% with cabozantinib versus 5% with everolimus (P<0.001). An interim analysis showed a trend toward longer OS with cabozantinib (hazard ratio for death 0.67, 95% CI 0.51–0.89, P=0.005), but the significance boundary was not crossed. Adverse events were managed with dose reductions, with 60% of cabozantinib patients and 25% of everolimus patients requiring dose reductions. Discontinuation due to adverse events occurred in 9% of cabozantinib and 10% of everolimus patients. Cabozantinib demonstrated a favorable safety profile, with common adverse events including diarrhea, fatigue, and hypertension. Everolimus was associated with higher rates of pneumonitis, anemia, and hyperglycemia. The trial design allowed for appropriate statistical power for PFS and OS, with a "trial within a trial" approach to evaluate PFS in the first 375 patients. Cabozantinib showed significant efficacy in patients who had previously received only one VEGFR inhibitor, with a median PFS of 9.1 months versus 3.7 months with everolimus. The study highlights cabozantinib's superior PFS compared to everolimus in RCC patients who have progressed after VEGFR-targeted therapy. The results suggest that cabozantinib may be a more effective second-line treatment for RCC. The trial was funded by Exelixis and conducted in accordance with Good Clinical Practice guidelines. The study was approved by institutional review boards and monitored by an independent data monitoring committee. The authors vouch for the accuracy and completeness of the data and for the fidelity of the study to the protocol. The study was published in the New England Journal of Medicine.The METEOR trial compared cabozantinib and everolimus in patients with advanced renal-cell carcinoma (RCC) that had progressed after VEGFR-targeted therapy. A total of 658 patients were randomly assigned to receive either cabozantinib (60 mg/day) or everolimus (10 mg/day). The primary endpoint was progression-free survival (PFS), with secondary endpoints including overall survival (OS) and objective response rate (ORR). Cabozantinib showed significantly longer PFS than everolimus, with median PFS of 7.4 months versus 3.8 months (hazard ratio 0.58, 95% CI 0.45–0.75, P<0.001). The ORR was 21% with cabozantinib versus 5% with everolimus (P<0.001). An interim analysis showed a trend toward longer OS with cabozantinib (hazard ratio for death 0.67, 95% CI 0.51–0.89, P=0.005), but the significance boundary was not crossed. Adverse events were managed with dose reductions, with 60% of cabozantinib patients and 25% of everolimus patients requiring dose reductions. Discontinuation due to adverse events occurred in 9% of cabozantinib and 10% of everolimus patients. Cabozantinib demonstrated a favorable safety profile, with common adverse events including diarrhea, fatigue, and hypertension. Everolimus was associated with higher rates of pneumonitis, anemia, and hyperglycemia. The trial design allowed for appropriate statistical power for PFS and OS, with a "trial within a trial" approach to evaluate PFS in the first 375 patients. Cabozantinib showed significant efficacy in patients who had previously received only one VEGFR inhibitor, with a median PFS of 9.1 months versus 3.7 months with everolimus. The study highlights cabozantinib's superior PFS compared to everolimus in RCC patients who have progressed after VEGFR-targeted therapy. The results suggest that cabozantinib may be a more effective second-line treatment for RCC. The trial was funded by Exelixis and conducted in accordance with Good Clinical Practice guidelines. The study was approved by institutional review boards and monitored by an independent data monitoring committee. The authors vouch for the accuracy and completeness of the data and for the fidelity of the study to the protocol. The study was published in the New England Journal of Medicine.