Raphael J, et al. - Herein, the sunitinib dose-escalation in terms of its efficacy and toxicity was contemplated, in mRCC patients progressing on the standard 50 mg dose. A clinical advantage could be gained along with prolonged survival from the dose-escalation with acceptable toxicity profiles. In order to overcome the drug resistance and to postpone the change in systemic therapy at progression, advanced studies were required.

Methods

• The design of this study was a single-institution retrospective review.
• It consisted of mRCC patients, treated outside trials with a 50 mg sunitinib dose given on an individualized schedule between October 2009 and January 2016, who subsequently progressed on imaging.
• The eligible candidates included all progressing patients who were dose-escalated to 62.5 and 75 mg on an individualized schedule if toxicity permitted.
• The Kaplan-Meier method gauged the median progression-free survival (PFS) and overall survival (OS).
• PFS1 and 2 were defined as the time between the start of sunitinib and first progression and the time between dose-escalation and second progression respectively.

Results

• 25 patients were enrolled with a median follow-up of 40.3 months (Q1-Q3: 11.1-66.6) and a mean age of 54 years (standard deviation: 12.4).
• Maximum patients underwent cytoreductive surgery (92%) and were men (88%). 32%, 44%, and 24% reported a good, intermediate, and poor prognostic Heng Score, respectively.
• At standard doses, 60% and 16% of patients displayed a partial response (PR) and a stable disease (SD) as best response respectively for a median duration of 11.4 months (95% CI: 3–20.7).
• Progressive disease as best response was noted in 6 patients (24%). Following the progression, 36% and 28% illustrated PR and SD on higher doses of sunitinib respectively for a median duration of 7.8 months (95% CI: 6.3-12.4).
• The median PFS1, PFS2 and OS were 6.1 months (95% CI: 2.3-19.4), 6.7 months (95% CI: 3.1-8.4) and 63.7 months (95% CI: 26-NR) respectively.
• Fatigue (56%), diarrhea (40%) and skin toxicity (28%) were discovered to be the most common adverse events after dose-escalation.