Management of hand-foot skin reaction (HFSR)/hand-foot syndrome (HFS) in SOLTI-0701: A double-blind, randomized phase IIb study comparing sorafenib (SOR) versus placebo (PL) in combination with capecitabine (CAP) in patients (pts) with advanced breast cancer (BC).

Abstract

1083 Background: We reported data from SOLTI-0701 demonstrating a clinical benefit with the oral regimen of SOR+CAP vs. PL+CAP in pts with advanced BC for progression-free survival (median, 6.4 vs. 4.1 mo; hazard ratio 0.58; 1-sided p=0.0006). Toxicities were comparable between treatment arms except for HFSR/HFS, which was not unexpected as HFSR and HFS are associated with SOR and CAP, respectively. Here we describe HFSR/HFS toxicity during this study. Methods: SOLTI-0701 is a multinational (Brazil, France, Spain) phase 2b study in HER2-negative pts with locally advanced or metastatic BC and ≤1 prior chemo regimen for advanced BC (n=229). Pts were randomized (1:1) to receive CAP (1,000 mg/m2 po, twice daily [BID], 14 of every 21 days) with PL or SOR (400 mg po, BID). The protocol recommended managing HFSR/HFS with symptomatic therapy, study drug (SOR, PL, CAP) interruption for grade (G) 2 toxicity, study drug interruption and dose reduction for recurrent G2 or G3 toxicity, and discontinuation for persistent G2/G3 toxicity. Results: Incidence of HFSR/HFS for SOR+CAP vs. PL+CAP was 89% vs. 63% for any grade and 45% vs. 13% for G3; Kaplan-Meier estimate of median time to onset for first incidence of any grade was 14 and 64 days, respectively. In the SOR+CAP arm, 48% and 78% of pts required SOR and CAP dose reductions, resulting in mean daily doses of 603 mg and 1485 mg/m2, respectively; mean number of cycles was 7.7 and 7.5, respectively. In the PL+CAP arm, 11% and 32% of pts required PL and CAP dose reductions, resulting in mean daily doses of 749 mg and 1,850 mg/m2, respectively; mean number of cycles was 6.5 and 6.6, respectively. HFSR/HFS led to treatment discontinuation in 8 pts (7.0%) for SOR+CAP and 2 pts (1.8%) for PL+CAP. Conclusions: Despite high incidence of HFSR/HFS, few pts discontinued treatment due to HFSR/HFS. Dose attenuation for both treatment agents was effective. More proactive management may reduce event duration and severity. In view of the PFS benefit, a phase 3 registration trial will commence in 2010 evaluating the combination of SOR+ CAP for advanced BC. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Onyx Pharmaceuticals