Impact of dose reduction on survival in patients starting sunitinib (SU) or pazopanib (PA) as first-line for metastatic renal cell carcinoma (mRCC).

Abstract

553 Background: SU and PA are both VEGFR TKI approved for treatment of mRCC. Previous studies reported that the reduced dose (RD) is not recommended for the beginning of therapy (Motzer et al. 2012) and suggested a direct correlation between dose and effectiveness of therapy (Houk et al. 2010). We aim to investigate if patients (pts) that decreased the dose during treatment have different outcomes compared to those who continue a standard dose (SD). Methods: All pts affected by mRCC who started SU or PA at SD have been included. Pts were divided into two groups: RD and SD, based on whether they reduced the therapy or not. The main reasons for dose change have been collected and the RD group was defined into 2 levels (1st level: SU37.5mg/d, 4/2 or PA 600mg/d; 2nd level: SU25mg/d, 4/2 or PA 400mg/d). Pts were stratified by IMDC prognostic criteria and differences in pts’ characteristics between RD and SD groups were evaluated as well as median PFS and OS. Results: A total of 280 pts have been included. Median age was 62y and 68% was male; 54% had good prognosis, 40% intermediate and 6% poor. First-line was SU in 84% and PA in 16% of cases. A total of 123 (44%) pts decreased the dose to first- (89%) or second-level (11%). The main reasons were hand-foot syndrome (17.9%), diarrhea (15.4%) asthenia (14.6%), mucositis (13.0%) and thrombocytopenia (11.4%). Significant differences between RD and SD groups were the female sex (40% vs. 25%; p = 0.01) and the rate of primary refractory disease (11% vs. 31%: p < 0.001). Median PFS and OS were 12.4 and 34.9 mos, respectively. In RD group, the median time before dose reduction was 3.5 mos. Excluding the primary refractory pts, median PFS was 18.6 and 15.0 mos (p = 0.06) and median OS was 68.0 and 40.7 mos (p = 0.14) in RD and SD group, respectively. In RD group, no differences between 1st- and 2nd-level of dose were observed both in PFS (11.0 vs. 13.1 mos; p = 0.82) and OS (42.8 vs. 36.0 mos; p = 0.78) after reduction. Conclusions: Dose reduction is a frequent event in pts who started a first-line therapy with SU or PA. This study reports that DR does not affect the survival of pts who initially started SU and PA at standard dose.