Continuous daily dosing (CDD) of sunitinib malate (SU) compares favorably with intermittent dosing in pts with advanced GIST

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10015 Background: SU, an oral multitargeted tyrosine kinase inhibitor of KIT, PDGFRs, VEGFRs, RET and FLT3, is approved multinationally for the treatment of imatinib (IM)-resistant or -intolerant GIST. SU 50 mg/d on a 4/2 schedule (6-wk cycles: 4 wks on treatment, 2 wks off) has demonstrated efficacy and acceptable tolerability in pts with advanced IM-resistant GIST. The current study assesses the efficacy and safety of CDD of SU in this pt population. Methods: In this multicenter phase (ph) II trial, pts with IM-resistant/intolerant GIST were randomized to receive morning or evening dosing of SU 37.5 mg daily. The primary endpoint was clinical benefit rate (CBR; percentage of pts with confirmed CR, PR or SD for =24 wks per RECIST). Investigator-assessed efficacy and safety data compiled in this ph II study and an earlier ph III study were compared informally, and the PK of SU and its metabolite were also analyzed. Results: Of 61 pts randomized, 60 received treatment with SU (30 pts/arm; ITT population). At a median duration on study of 30 wks (range: 4–52+), 33 pts remain on study and 27 have discontinued. The SU dose was reduced to 25 mg/d in 9 pts due to AEs. The most common non-hematologic AEs of any cause (primarily grade [gr] 1/2) were diarrhea (40%), asthenia (38%) and fatigue (35%). Gr 3 AEs were asthenia (13%), fatigue (7%) and diarrhea (7%); gr 4 abdominal pain was reported in 3% pts. Hematologic toxicities included gr 3 anemia (10%), neutropenia (17%, all non-febrile) and thrombocytopenia (7%) and gr 4 anemia (3%). Toxicities were similar in the morning and evening dosing groups. Preliminary PK data indicated no unexpected accumulation with CDD. To date, median PFS is 27 wks (CI: 24–41) and overall CBR is 24%, including 11% pts with PRs, which compares favorably with results obtained with the approved regimen of SU 50 mg/d on the 4/2 schedule (N=207; PR: 7%; CBR: 25%; PFS 28 wks [CI: 14–34]; phase III study). Conclusions: SU is well tolerated and clinically active when given as 37.5 mg CDD in pts with IM- resistant/-intolerant GIST. The AE profile for SU CDD appears similar to that of the 4/2 schedule. Morning and evening dosing seem to have similar tolerability. SU CDD appears to be a safe and effective alternative dosing strategy for pts with IM-resistant/intolerant GIST. No significant financial relationships to disclose.