Clinical Effect of Dose-Escalation after Disease Progression in Patients with Metastatic Renal Cell Carcinoma

Abstract Background Given the variability in drug levels with tyrosine kinase inhibitors (TKI) in patients with metastatic renal cell carcinoma (mRCC), dose escalation at the time of progressive disease (PD) may have anti-tumor effect. Patients and Methods Patients with mRCC who were treated at Cleveland Clinic with TKIs and were dose-escalated following PD per RECIST 1.1 were retrospectively reviewed. Patient and disease-related data were collected and summarized as frequency counts and percentages, or medians and ranges. The Kaplan-Meier method was used to summarize treatment duration on escalated doses. Results Twenty-two patients were identified. The majority of patients (82%) were male; median age at diagnosis was 58 (range, 40-71). The most common histology was clear cell (73%). Axitinib was the most frequently escalated agent following PD (17 patients), followed by sunitinib (3 patients), and pazopanib (2 patients). Prior to PD, the median treatment duration was 6.8 months (range, 1.6-50.6). Of patients with evaluable tumor measurements after dose escalation (n=18), 14 patients (78%) had a decrease in tumor burden. Median decrease in tumor burden after dose-escalation was 14% (range, 2-58%); 4 (22%) patients had decreases > 10%, 2 (11%) > 20%, and 4 (22%) >30% (RECIST PR). Five patients (23%) continue to be treated at escalated doses. The median duration of escalated therapy is estimated to be 10.1 months (range, 0.6 to 37.9 months). Conclusions Dose-escalation of TKIs after PD in select mRCC patients can lead to reduction in tumor burden and extend the duration of therapy.