Positive data have been reported from subgroup analyses of a phase III pivotal trial comparing cabozantinib (Cometriq, Exelixis, Inc.) with everolimus (Afinitor, Novartis) in 658 patients with renal cell carcinoma (RCC) who have experienced disease progression after treatment with a vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor (TKI).
Treatment with cabozantinib improved both progression-free survival (PFS), the trial’s primary endpoint, and the objective response rate (ORR), a secondary endpoint, across various prespecified and post hoc analysis subgroups. The observed benefits were independent of the location and number of organ metastases; the patient’s tumor burden; the type, duration, and number of prior VEGF receptor TKI therapies; and prior programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) therapy.
The new findings will be presented on January 9 at the American Society of Clinical Oncology (ASCO) 2016 Genitourinary Cancers Symposium in San Francisco, California.
As previously reported, the pivotal METEOR trial met its primary endpoint of demonstrating a statistically significant increase in PFS for cabozantinib compared with everolimus, as determined by an independent radiology committee. The primary analysis was conducted among the first 375 patients randomized to ensure sufficient follow-up and a PFS profile that would not be primarily weighted toward early events. The median PFS in this population was 7.4 months for the cabozantinib arm compared with 3.8 months for the everolimus arm, corresponding to a 42% reduction in the rate of disease progression or death for cabozantinib compared with everolimus (hazard ratio [HR] = 0.58; P < 0.001). These data were published in the New England Journal of Medicine.
The ASCO presentation will be the first to include PFS findings from the METEOR trial’s entire 658-patient study population. As assessed by an independent radiology committee, the median PFS across all enrolled patients was 7.4 months for the cabozantinib arm compared with 3.9 months for the everolimus arm, corresponding to a 48% reduction in the rate of disease progression or death for cabozantinib compared with everolimus (HR = 0.52; P < 0.001).
Updated ORR results from the full 658-patient study population will also be presented at the ASCO meeting for the first time. As assessed by an independent radiology committee, the ORR across all 658 patients was 17% for cabozantinib and 3% for everolimus. The median duration of response for cabozantinib was not reached compared with 7.4 months for everolimus. As reported in September 2015, the ORR for the first 375 patients enrolled was 21% for cabozantinib and 5% for everolimus.
For patients without prior PD-1/PD-L1 therapy, the median PFS was 7.4 months for cabozantinib and 3.9 months for everolimus (HR = 0.54). For patients who had received prior PD-1/PD-L1 therapy, the median PFS for cabozantinib was not reached, and the median PFS for everolimus was 4.1 months (HR = 0.22).
As previously reported, data pertaining to overall survival (OS) in the entire study population of 658 patients, a secondary endpoint, were immature at the data cutoff. A prespecified interim analysis triggered by the primary analysis for PFS showed a strong trend in OS favoring cabozantinib (HR = 0.67; P =0.005). At the time of the interim analysis, the P value of 0.0019 to achieve statistical significance was not reached, and the trial will continue to the final analysis of OS anticipated in 2016.
Cabozantinib inhibits the activity of tyrosine kinases, including MET, VEGF receptors, AXL, and RET. These receptor tyrosine kinases are involved in both normal cellular functions and pathologic processes, such as oncogenesis, metastasis, tumor angiogenesis, and the maintenance of the tumor microenvironment.
Cabozantinib is currently approved in the U.S. for the treatment of patients with progressive, metastatic medullary thyroid cancer. It is not indicated for patients with RCC.
Source: Exelixis, Inc.; January 4, 2016.