Cabozantinib (Cabometyx) was more effective than everolimus (Afinitor) in patients with advanced renal cell carcinoma and bone metastases, according to a subgroup analysis of a pivotal clinical trial.
Data from that trial, called METEOR (Metastatic Renal Cell Carcinoma Phase III Study Evaluating Cabozantinib vs Everolimus), showed that progression-free survival in patients with bone metastases was 7.4 months with cabozantinib versus 2.7 months with everolimus (HR 0.33; 95% CI 0.21-0.51), said Bernard Escudier, MD, of the Gustave Roussy Institute in Villejuif Cedex, France, and colleagues.
Median overall survival was also significantly longer with cabozantinib in patients with bone metastases (20 versus 12 months; HR 0.54; 95% CI 0.34-0.84), as was the objective response rate (17% versus 0%), the team reported online in the Journal of Clinical Oncology.
Improved progression-free survival, overall survival, and objective response rates were also found in patients on cabozantinib without bone metastases, the study authors noted.
“Bone metastases are associated with a poor prognosis in advanced renal cell carcinoma, and additional treatments for these patients are needed. Cabozantinib is a standard of care for previously treated patients with advanced renal cell carcinoma, with clinical benefits in progression-free survival, overall survival, and objective response rates that are observed irrespective of the presence of bone metastases. On the basis of these outcomes, cabozantinib represents a good treatment option for this difficult-to-treat patient population.”
However, one expert was less than impressed with the results of the analysis: Asked for his opinion, Brian Rini, MD, of the Cleveland Clinic, who was not involved with the study, told MedPage Today: “What this study really shows is that renal cell carcinoma patients do worse on everolimus, not that they do better on cabo. The response rate and median progression-free survival on cabo are identical in patients with and without bone metastases. Because everolimus patients with bone metastases do worse, the relative advantage is greater.
“As these are unplanned, post-hoc subset analyses, they need to be interpreted with extreme caution,” he said via email. “There may be a rationale to give cabo to renal cell carcinoma patients with bone metastases, but it requires additional prospective study to make definitive statements.”
In the study, 658 patients were randomly assigned 1:1 to receive either cabozantinib or everolimus from August 2013 to November 2014. Of these patients, 142 (22%) had bone metastases at baseline: 77 in the cabozantinib group and 65 in the everolimus group. Of the patients with bone metastases, 112 (79%) also had visceral metastases: 60 in the cabozantinib group and 52 in the everolimus group. Overall, baseline characteristics were similar in patients with and without bone metastases and between treatment groups.
The bone scan response was 20% (95% CI 12%-29%) in the cabozantinib group and 10% (95% CI 4%-20%) in the everolimus group. Bone biomarkers changed more in the cabozantinib group, including decreases in the bone formation marker PINP (procollagen type I N-terminal propeptide) and the bone resorption marker CTx (C-terminal telopeptide of type 1 collagen). The use of bone-targeted therapies was similar in both groups, which suggests that the changes were caused by the study treatment, Escudier and colleagues explained.
“Changes in bone biomarkers with cabozantinib may be a result of a general pharmacodynamic effect, because these changes were observed in both patients with bone metastases and those without bone metastases. Cabozantinib treatment has also been associated with a reduction in the levels of bone biomarkers in patients with prostate cancer and bone metastases, consistent with these results.”
Safety in patients with bone metastases was consistent with the safety profiles in the overall study population for both treatments, the team reported. In the cabozantinib group, common grade 3 or 4 adverse events included fatigue, diarrhea, and palmar-plantar erythrodysesthesia syndrome. In the everolimus group, adverse events were anemia, hyperglycemia, and lymphocytopenia.
“Bone metastases are associated with a poor prognosis and a reduced benefit from targeted therapies in patients with renal cell carcinoma,” the researchers concluded. “Although our study was not powered for statistical testing of the subgroup analyses, the values of the hazard ratios and medians for progression-free survival and overall survival for patients with bone metastases were notable and favored cabozantinib over everolimus.”
The study was funded by Exelixis.
Escudier reported financial relationships with Pfizer, Novartis, Bayer AG, Bristol-Myers Squibb, Ipsen, Exelixis, and Roche/Genentech.
Rini reported having no financial relationships.
F. Perry Wilson, MD, MSCE Assistant Professor, Section of Nephrology, Yale School of Medicine and Dorothy Caputo, MA, BSN, RN, Nurse Planner