Efficacy and safety of a reduced starting dose of cabozantinib (20 mg) plus nivolumab for renal cell carcinoma in real-world practice

In systemic treatment for renal cell carcinoma, some patients require dose reduction to prevent adverse events. However, there is currently almost no evidence to support a reduced starting dose for cabozantinib + nivolumab (C + N) in clinical practice. We retrospectively analyzed single-institution data for patients with renal cell carcinoma with an assessed response to C + N. The starting dose was determined during a multidisciplinary meeting for each patient by considering the following patient characteristics: age, performance status, body weight, and medical history. In all cases, the dosage and schedule of nivolumab could not be modified. Efficacy and adverse events were examined. Fourteen and eighteen patients, respectively, received 20 (reduced dose) and 40 mg (standard dose) of cabozantinib in C + N treatment. The median age was 79.5 years in the reduced-dose group and 69.5 years in the normal-dose group (P < .0001). The objective response rate was 71% in the reduced-dose group and 78% in the normal-dose group (P = .6807). There were no significant differences in progression-free survival and overall survival, nor in the overall and grade ≥ 3 adverse events rates between the groups. Liver dysfunction of any grade occurred significantly more frequently in the normal-dose group (61%) versus the reduced-dose group (21%) (P = .0247). A 20-mg starting dose of cabozantinib in C + N therapy can achieve almost the same efficacy as a normal starting dose for patients who are hesitant to start treatment at the normal 40-mg dose.