In the METEOR trial (NCT01865747), cabozantinib showed a statistically significant improvement in progression-free survival (PFS) compared with everolimus in patients with previously treated RCC (median 7.4 vs 3.8 months; HR=0.58, 95% CI 0.45–0.75; P<0.001) and improved the objective response rate. Here we present the final OS results from a second interim analysis.
Patients with measurable clear cell RCC, KPS ≥70, and ≥1 prior VEGFR TKI were randomised 1:1 to cabozantinib (60 mg qd) or everolimus (10 mg qd) stratified by MSKCC risk group and number of prior VEGFR TKIs (1 or ≥2). The study was designed to detect a HR for OS of 0.75 (80% power, 2-sided α=0.04).
From Aug 2013–Nov 2014, 658 pts were randomised. As of 31 Dec 2015, with a minimum follow-up of 13 months, 320 deaths were recorded (140 for cabozantinib and 180 for everolimus). 74 (22%) patients remained on therapy in the cabozantinib arm vs 25 (8%) patients in the everolimus arm. The secondary endpoint of improved OS for cabozantinib-treated patients was met. Median OS was 21.4 months for cabozantinib vs 16.5 months for everolimus, with a 33% reduction in the rate of death (HR 0.67, 95% CI 0.53 to 0.83, P=0.0003). Landmark estimates of survival at 18 months were 58% in the cabozantinib arm vs 47% of the everolimus arm. OS benefit with cabozantinib was observed across all prespecified subgroups including MSKCC risk group, number/type of prior VEGFR TKIs, prior anti-PD-1/PD-L1 treatment, location/extent of tumor metastases, and tumor MET expression level. Serious adverse events (SAEs) were consistent with the safety profile previously reported.
Cabozantinib is the only agent to demonstrate a significant benefit in OS, PFS, and ORR in a Phase 3 trial in this patient population. Cabozantinib is an important new treatment option for these patients.