Cabozantinib Dose Reductions May Indicate Adequate Dose Exposure Among Patients With Metastatic Renal Cell Carcinoma

Patients with metastatic renal cell carcinoma who experienced a dose reduction with cabozantinib had a significantly better overall survival and time to treatment failure.

Jeffrey Graham, MD, MPH, CancerCare Manitoba at University of Manitoba, Winnipeg, Canada, and coauthors explained, “The association between toxicity and therapeutic effectiveness has been established with other [tyrosine kinase inhibitors] TKIs.”

There were 319 patients treated with cabozantinib in the second line or later were included in this study from the Canadian Kidney Cancer Information System. Patients were categorized based on those who needed a dose reduction and those who did not. Outcomes were objective response rate (ORR), time to treatment failure (TTF), and overall survival (OS).

Of the 319 patients included, 48.3% underwent a dose reduction. There was no significant difference between the response rates of those who required a dose reduction and those who did not (15.1% vs 18.2%; P = .55). The OS (26.15 months vs 15.47 months; P = .19) and TTF (12.74 months vs 6.44 months; P = .022) of patients who underwent dose reductions was superior to those of patients who did not undergo dose reductions. After adjusting for International mRCC Database Consortium (IMDC) risk group, the benefit seen in the group with dose reductions remained significant for these outcomes. The initial cabozantinib dose did not have an impact on ORR, OS, or TTF.

This study demonstrated the association between cabozantinib dose reductions due to toxicity and improved survival and time to treatment failure among patients with metastatic renal cell carcinoma. Dr Graham et al concluded, “These findings underscore the potential of using on-treatment toxicity as an indicator of adequate drug exposure to individualize dosing and optimize treatment effectiveness.” 

Source:

Graham J, Ghosh S, Breau RH, et al. Association of cabozantinib dose reductions for toxicity with clinical effectiveness in metastatic renal cell carcinoma (mRCC): Results from the Canadian Kidney Cancer Information System (CKCis). Clin Genitourin Cancer. Published online February 22, 2024. doi:10.1016/j.clgc.2024.02.011.