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Early Intermittent Cabozantinib in Metastatic Renal Cell Carcinoma: Efficacy and Safety in a Multicenter
Raphaelle Dermine1, Julie Harmant1, Marco Gizzi2
1Department of Medical Oncology, Institut Roi Albert II, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
Background:
Cabozantinib is active in metastatic clear-cell renal cell carcinoma (mccRCC), but its use is often limited by treatment-related toxicity. We evaluated toxicity-guided intermittent cabozantinib strategy introduced early during treatment in patients initially started at 60 mg/day.
Patients And Methods:
We conducted a retrospective multicenter study including patients with mccRCC treated with single-agent cabozantinib in the second- or third-line setting. Patients were classified into three cohorts: continuous 60 mg starting dose (cohort A), continuous 40 mg starting dose (cohort B), and 60 mg with early switch to a toxicity-guided early intermittent 5 days-on/2 days-off schedule at the onset of selected grade 2 toxicities (cohort C). The primary endpoints were progression-free survival (PFS) and grade 3-4 cabozantinib-related toxicity.
Results:
Sixty-one patients were included: 20 in cohort A, 21 in cohort B, and 20 in cohort C. The objective response rate was 40%, 29%, and 40% in cohorts A, B, and C, respectively. Median PFS was 9.5, 7.0, and 12.0 months, and median OS was 20.0, 15.0, and 24.0 months, respectively. Grade 3 adverse events occurred in 70% of patients in cohort A, 52% in cohort B, and 50% in cohort C. Dose reductions occurred in 70%, 19%, and 45%, respectively, and median time to first dose reduction was 3 months in cohort A versus 9 months in cohorts B and 7 months in cohort C.
Conclusions:
Early intermittent cabozantinib dosing appeared feasible and was associated with improved tolerability compared with continuous 60-mg dosing, without an apparent loss of antitumor activity. These retrospective findings should be interpreted as hypothesis-generating and warrant prospective evaluation.
