Evaluation of soluble KIT (sKIT) as a potential surrogate marker for TTP in sunitinib malate (SU)-treated patients (pts) with advanced GIST

10007 Background: SU is an oral, multitargeted tyrosine kinase inhibitor of KIT, PDGFRs, VEGFRs, RET and FLT3, approved multinationally for the treatment of imatinib (IM)-resistant/-intolerant GIST. Preliminary analysis in a SU phase I/II GIST study suggested that a decline in plasma sKIT levels may correlate with measures of clinical benefit. We evaluated the potential of sKIT as a surrogate marker for TTP using samples obtained in a randomized, double-blind, placebo-controlled phase III study of SU in pts with IM-resistant/-intolerant GIST, clinical results of which have been reported previously. Methods: 312 pts were randomized (2:1) to receive SU 50 mg (n=207) or placebo (n=105) daily in 6-wk cycles (4 wks on treatment, 2 wks off), respectively. The primary endpoint was TTP as per RECIST. Levels of sKIT in plasma samples were measured in cycle 1 on days 1, 14 and 28 and in cycles 2 and 3 on days 1 and 28 using a performance-validated ELISA. Prentice Criterion, Cox models and the Proportion of Treatmen...