Sunitinib Dose Escalation in Metastatic Renal Cell Carcinoma

Background and objective: Sunitinib has been a standard treatment for patients with metastatic renal cell carcinoma (mRCC) since 2006. However, almost all patients will eventually progress. Besides well described mechanisms of primary or secondary resistance, insufficient drug exposure may lead to disease progression. The aim of this study was to identify patients in whom sunitinib dose escalation was performed and to analyse safety and efficacy of this strategy in clinical practice. Methods: A single-centre retrospective study on dose escalation in mRCC patients who were treated with sunitinib at the Medical University of Vienna between January 2011 and May 2016. Dose escalation was studied in patients who had either progressed (cohort 1: PD) or had stable disease with minor progression (cohort 2: SD). The primary endpoints were response rate before and after dose escalation, global progression free survival and overall survival. Secondary endpoints were treatment duration before and after dose escalation and toxicity. Results: Dose escalation up to 75 mg was offered in 21 out of 265 patients. Response rates before and after dose escalation were 42,8% and 23.8%, respectively. The median global PFS and OS were 15.60 and 32.95 months, respectively. The median treatment duration before and after dose escalation was 6.1 months (1.3–29.3 months) and 6.6 months (2.5–16.6 months). No new toxicities emerged under escalated dose and no grade 4 adverse events occurred. Conclusion: Sunitinib dose escalation may be a strategy in patients with few toxicities at the time point of progression.