Cabozantinib, a New Standard of Care for Patients With Advanced Renal Cell Carcinoma and Bone Metastases? Subgroup Analysis of the METEOR Trial

Abstract

Purpose Cabozantinib, an inhibitor of tyrosine kinases including MET, vascular endothelial growth factor receptors, and AXL, increased 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 the phase III METEOR trial. Because bone metastases are associated with increased morbidity in patients with RCC, bone-related outcomes were analyzed in METEOR. Patients and Methods Six hundred fifty-eight patients were randomly assigned 1:1 to receive 60 mg cabozantinib or 10 mg everolimus. Prespecified subgroup analyses of PFS, OS, and ORR were conducted in patients grouped by baseline bone metastases status per independent radiology committee (IRC). Additional end points included bone scan response per IRC, skeletal-related events, and changes in bone biomarkers. Results For patients with bone metastases at baseline (cabozantinib [n = 77]; everolimus [n = 65]), median PFS was 7.4 months for cabozantinib versus 2.7 months for everolimus (hazard ratio, 0.33 [95% CI, 0.21 to 0.51]). Median OS was also longer with cabozantinib (20.1 months v 12.1 months; hazard ratio, 0.54 [95% CI, 0.34 to 0.84]), and ORR per IRC was higher (17% v 0%). The rate of skeletal-related events was 23% with cabozantinib and 29% with everolimus, and bone scan response per IRC was 20% versus 10%, respectively. PFS, OS, and ORR were also improved with cabozantinib in patients without bone metastases. Changes in bone biomarkers were greater with cabozantinib than with everolimus. The overall safety profiles of cabozantinib and everolimus in patients with bone metastases were consistent with those observed in patients without bone metastases. Conclusion Cabozantinib treatment was associated with improved PFS, OS, and ORR when compared with everolimus treatment in patients with advanced RCC and bone metastases and represents a good treatment option for these patients.

Trial registration: ClinicalTrials.gov NCT01865747.

Figures

Fig 1.

Patient disposition as of December 31, 2015. Disposition for the overall population has been published. (*) One patient assigned to everolimus received cabozantinib. ORR, objective response rate; OS, overall survival; PFS, progression-free survival.

Fig 2.

Kaplan-Meier plots of progression-free survival (PFS). Disease progression was assessed by an independent radiology committee. Data are through May 22, 2015.

Fig 3.

Kaplan-Meier analyses of overall survival (OS). Data are through December 31, 2015. NE, not estimable.

Fig 4.

Effects on bone biomarkers. The bar shows the 25% to 75% quartiles, and the line shows the median. The range and number of patients (n) are listed below the graph. Baseline measurements were taken before the first dose. All available baseline patient data were included regardless of whether corresponding data were available at week 5 or week 9. BSAP, bone-specific alkaline phosphatase; CTx, C-terminal cross-linked telopeptides of type 1 collagen; P1NP, N-terminal propeptide of type 1 collagen.