Cabozantinib (Cabometyx) was associated with an improvement in overall survival and progression-free survival compared with everolimus (Afinitor) in pretreated patients with advanced RCC with bone metastases at baseline.
Bernard Escudier, MD
Cabozantinib (Cabometyx) was associated with an 8-month improvement in overall survival (OS) and a 4.7-month improvement in progression-free survival (PFS) compared with everolimus (Afinitor) in pretreated patients with advanced renal cell carcinoma (RCC) with bone metastases at baseline.1
In a subgroup analysis of the phase III METEOR trial, the median OS in patients with baseline bone metastases was 20.1 months with cabozantinib versus 12.1 months with everolimus (HR, 0.54; 95% CI, 0.34-0.84). The median PFS was 7.4 versus 2.7 months, respectively (HR, 0.33; 95% CI, 0.21-0.51), and ORR was 17% versus 0%, respectively.
“Bone metastases are associated with a poor prognosis in advanced RCC, and additional treatments for these patients are needed. On the basis of these outcomes, cabozantinib represents a good treatment option for this difficult-to-treat patient population,” corresponding author Bernard Escudier, MD, Institut Gustave Roussy, France, and colleagues wrote.
Based on the overall results from the METEOR trial, cabozantinib was approved by the FDA in April 2016 for the treatment of patients with advanced RCC following prior antiangiogenic therapy. METEOR included 658 patients with clear cell RCC who were randomized to 60 mg daily of cabozantinib (n = 330) or 10 mg of daily everolimus (n = 328).
The median OS in the overall population was 21.4 months with cabozantinib versus 16.5 months for with everolimus (HR, 0.66; P = .0003). The median PFS was 7.4 months versus 3.9 months, respectively (HR, 0.51; P <.0001).2
Seventy-seven patients in the cabozantinib arm and 65 in the control arm had bone metastases at baseline. The median patient agent was 61 years (range, 32-84) versus 64 years (range, 34-84), respectively.
Roughly 65% of patients in each arm had received 1 prior VEGFR TKI, with 35% of those assigned to cabozantinib and 34% of those in the everolimus group receiving ≥2 prior VEGFR TKIs. Use of prior VEGFR TKIs included sunitinib (Sutent; 61% in the cabozantinib arm vs 59% in the everolimus arm), pazopanib (Votrient; 46% vs 48%), axitinib (Inlyta; 22% vs 23%), and sorafenib (7% vs 11%).
The rates of prior nivolumab (Opdivo) and bevacizumab (Avastin) between the cabozantinib and everolimus arms were similar as well, at 5% versus 6%, and 3% versus 6%, respectively. The rates of external-beam radiation therapy and nephrectomy were 53% versus 60%, and 87% versus 72%, respectively. Thirty percent of patients in the cabozantinib group had used bone-targeted therapies (bisphosphonates and denosumab) compared with 20% in the everolimus group.
For patients with bone metastases at baseline, 23% of patients in the experimental arm experienced on-study skeletal-related events (SREs) compared with 29% of those in the everolimus group. For patients who did not have bone metastases at baseline, the incidence of on-study SREs was 12% in the cabozantinib group and 10% in the everolimus group.
“The incidence of SREs, an exploratory endpoint of the study, was approximately 6% lower with cabozantinib than with everolimus for patients with bone metastases at baseline,” researchers wrote. “Patients in the cabozantinib group received treatment for a longer duration than did those in the everolimus group, which may have increased the observed incidence of SREs.”
The median duration of exposure for patients with bone metastases was 9.8 months (range, 1.0-23.2) for cabozantinib-treated patients and 3.7 months (range, 0.2-21.8) for everolimus-treated patients.
The incidence of grade 3/4 adverse events (AEs) in patients with bone metastases was 73% in the cabozantinib arm compared with 51% for patients receiving everolimus. Among patients treated with cabozantinib, grade 3/4 AEs included fatigue (16% vs 6% with everolimus), diarrhea (14% vs 0), palmar-plantar erythrodysesthesia syndrome (8% vs 0%), asthenia (6% vs 2%), hypertension (6% vs 2%), and nausea (6% vs 0%).