Patterns of PET response after long-term sunitinib therapy in patients (pts) with imatinib (IM)-resistant gastrointestinal stromal tumors (GIST)

Abstract

9547 Background: Sunitinib malate (previously known as SU11248) is an active therapy for GIST patients resistant to or intolerant of IM. During initial development, sunitinib was administered in 4–6 week cycles, with 2–4 weeks of drug dosing followed by 2 weeks off treatment. We previously reported suppression of tumor-related 18FDG avidity on PET imaging during sunitinib dosing, with rebound tumor uptake while off drug. This rebound, seen in 80% with initial PET suppression, did not correlate with lack of clinical benefit. We asked if this pattern persists in pts who benefited from long term (> 2 years) sunitinib therapy. Methods: Of 77 pts in our initial Phase I/II study, 7 remain on therapy with sunitinib for more than 2 years, 4 of whom had matched baseline PET and CT data to assess tumor metabolic activity on and off sunitinib dosing. PET scans were obtained at baseline, during initial treatment, during the off-treatment period, and again after > 2 years therapy. These 4 pts were followed for a median 39 months (range 35–45 months) and for a median of 35 cycles (range 27–47). Two achieved PR and two SD. Results: Initially, all 4 exhibited suppression of tumor FDG avidity with treatment followed by rebound during the off-treatment period. By 6 months, all showed complete suppression of FDG activity. After > 2 years on sunitinib, GIST lesions in 2 pts showed no activity on PET, even while off sunitinib, while GIST in 2 pts demonstrated rebound flare when off therapy. The GIST lesions have not progressed despite the transient metabolic rebound while off sunitinib. Conclusions: Metastatic lesions in pts with IM-resistant GIST benefiting from long-term sunitinib therapy display two patterns on PET imaging. GIST in certain pts who benefit from therapy demonstrates metabolic rebound of activity when off dosing, while lesions in other pts remain metabolically inert on PET even during the brief dosing breaks. Functional imaging may yield insights to differences in the underlying biology of GIST subtypes in different pts. [Table: see text]