Clinical Outcomes by Nephrectomy Status In METEOR, A Randomized Phase 3 Trial of Cabozantinib Versus Everolimus in Patients with Advanced Renal Cell Carcinoma

. Background: We investigated outcomes with cabozantinib versus everolimus in patients with advanced renal cell carcinoma (RCC) with or without prior nephrectomy in the phase 3 METEOR trial (NCT01865747). Methods: Patients (N=658) with advanced clear cell RCC and prior treatment with ≥ 1 VEGFR tyrosine kinase inhibitor (TKI) were randomized to cabozantinib 60mg/day or everolimus 10mg/day. Pre-specified subgroup analyses of progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were conducted by prior nephrectomy status. Response was assessed by independent radiology committee. Results: Most enrolled patients (85%) had prior nephrectomy. Baseline prognostic factors (e.g. MSKCC risk group) were less favorable for patients without prior nephrectomy. Cabozantinib improved outcomes versus everolimus in the subgroups with and without nephrectomy— hazard ratios (95% CIs) of 0.51 (0.41–0.64) and 0.51 (0.30–0.86), respectively, for PFS, and 0.66 (0.52–0.84) and 0.75 (0.44–1.27), respectively, for OS. Median OS was numerically longer in patients with versus those without prior nephrectomy in both treatment arms. ORR for cabozantinib versus everolimus was 17% versus 4% for the prior nephrectomy subgroup and 21% versus 2% for the subgroup without prior nephrectomy. Among evaluable patients without prior nephrectomy, reductions of renal target lesions occurred in 94% (16/17) of patients in the cabozantinib arm versus 44% (8/18) in the everolimus arm. The safety profiles of both subgroups were generally consistent with that of the overall study population. Conclusion: Cabozantinib improved PFS, ORR, and OS compared with everolimus in patients with advanced RCC irrespective of nephrectomy status.