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

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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.