Escudier B, et al. - In the phase III METEOR trial, cabozantinib, an inhibitor of tyrosine kinases including MET, vascular endothelial growth factor receptors, and AXL, resulted in an increase in progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) in patients with advanced renal cell carcinoma (RCC) after previous vascular endothelial growth factor receptor–targeted therapy. In view of the association of bone metastases with increased morbidity in patients with RCC, researchers analyzed bone-related outcomes in METEOR. Compared with everolimus treatment, cabozantinib treatment was associated with improved PFS, OS, and ORR in patients with advanced RCC and bone metastases. Cabozantinib treatment thus seemed a good treatment option for these patients.

Methods

• Researchers randomly assigned 658 patients (1:1) to receive 60 mg cabozantinib or 10 mg everolimus.
• In patients grouped by baseline bone metastases status per independent radiology committee (IRC), they conducted prespecified subgroup analyses of PFS, OS, and ORR.
• Bone scan response per IRC, skeletal-related events, and changes in bone biomarkers were assessed as the additional end points.

Results

• For patients with bone metastases at baseline (cabozantinib [n = 77]; everolimus [n = 65]), median PFS was 7.4 months vs 2.7 months with cabozantinib compared to everolimus (hazard ratio, 0.33 [95% CI, 0.21 to 0.51]), respectively.
• With cabozantinib, longer median OS (20.1 months vs 12.1 months; hazard ratio, 0.54 [95% CI, 0.34 to 0.84]), and higher ORR per IRC were observed (17% vs 0%).
• In this study, the rate of skeletal-related events was 23% with cabozantinib compared to 29% with everolimus, and bone scan response per IRC was 20% vs 10%, respectively.
• In patients without bone metastases, PFS, OS, and ORR were also improved with cabozantinib.
• In comparison with everolimus, changes in bone biomarkers were greater with cabozantinib.
• Patients with bone metastases had the overall safety profiles of cabozantinib and everolimus, consistent with those observed in patients without bone metastases.