Evaluation of hand-foot syndrome (HFS) as a potential biomarker of sunitinib (SU) efficacy in patients (pts) with metastatic renal cell carcinoma (mRCC) and gastrointestinal stromal tumor (GIST).

Abstract

e21113 Background: Common side effects of tyrosine kinase inhibitors (TKIs) such as SU include HFS and related skin toxicities. SU is a multitargeted inhibitor of VEGFR, PDGFR and KIT, and is standard of care for the treatment of advanced RCC and imatinib-resistant/intolerant GIST. In this retrospective analysis, correlations between SU-associated HFS and efficacy endpoints were investigated in mRCC and GIST pts from 5 and 4 clinical trials, respectively. Methods: Analyses included data from 1,186 pts with mRCC (n=770) or GIST (n=416) who received single-agent SU at 25, 50, or 75 mg/d on an intermittent schedule (4 weeks (wk) on/2 wk off, 2 wk on/2 wk off, or 2 wk on/1 wk off: n=869; 73%) or at 37.5 mg continuous daily dosing (n=317; 27%). Median progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier methods and compared between pts with vs. without HFS by log-rank test. ORR was compared by Pearson’s chi-square test. Tumor response was assessed by investigators and adverse events were recorded regularly. Multivariate, time-dependent covariate, and landmark analyses were performed. Results: Of 1,186 pts, 260 (22%) developed any-grade HFS, compared with 926 (78%) who did not. Pts with mRCC who developed HFS had significantly better ORR (66.5% vs. 31.8%), PFS (14.3 vs. 8.3 mo), and OS (38.3 vs. 18.9 mo) than pts who did not (P<0.0001). Pts with GIST who developed HFS also had significantly better ORR (22.2% vs. 10.7%), PFS (11.0 vs. 5.5 mo), and OS (35.7 vs. 16.6 mo) than pts who did not (P<0.01). SU-associated HFS remained a significant predictor of both PFS and OS in a multivariate analysis (and of OS by time-dependent covariate analysis) in both mRCC and GIST pts. In 6- and 12-wk landmark analyses, pts with mRCC but not GIST who developed HFS had significantly longer OS, with a trend toward longer PFS, than pts who did not. Conclusions: SU-associated HFS was associated with improved PFS and OS in both mRCC and GIST pts, although the landmark analysis suggests that HFS may not be a reliable biomarker of SU efficacy at early time points.