Early metabolic response to continuous daily dosing of sunitinib in soft tissue sarcomas (STS) other than GIST using FDG- PET

Abstract

10529 Background: Sunitinib malate is a multitargeted tyrosine kinase inhibitor of KIT, PDGFRs, VEGFRs, FLT3, CSF-1R and RET approved for the treatment of imatinib-resistant/intolerant GIST and advanced RCC on a dosing schedule of 50 mg/day for 4 weeks followed by 2 weeks off treatment. Previous studies of sunitinib as a single agent in advanced GIST have shown early metabolic response using FDG-PET. We report the metabolic FDG-PET response of STS patients to sunitinib dosed at 37.5 mg/day in continuous 4-week cycles in a two-center phase II trial. Methods: The primary endpoint in this study, involving patients with metastatic and/or locally advanced STS other than GIST, is RECIST-defined ORR. Early metabolic response was also assessed in a subset of patients using FDG-PET/CT scanning at baseline and 10–14 days after initiation of sunitinib. For each patient, maximum standardized uptake values (SUVmax) were measured in up to 5 lesions with the greatest FDG uptake; percent change in SUVmax of individual lesions as well as summed SUVmax of all lesions per patient were calculated relative to baseline. Metabolic response was assessed using SUVmax percent-change thresholds per EORTC criteria (PR ≤ - 25% < SD < +25% ≤ PD). Results: As of Jan. 2008, 41 patients were enrolled and had received treatment. Overall efficacy and safety results are reported by Keohan et al. (ASCO 2008). One patient achieved a RECIST-defined PR, which was detected by cycle 2. FDG-PET results available for 21 patients (86 lesions) showed metabolic PR in 40 lesions, SD in 40 and PD in 6. Overall metabolic responses were 10 PR, 11 SD and 0 PD. While there were no patients with metabolic PD based on the summed SUVmax, 2 patients had 2 lesions with PD and 2 patients had 1 lesion with PD suggesting that there was heterogeneous response/progression in 4/11 patients. A detailed comparison of metabolic response and anatomic response will be presented. Conclusions: Nearly half of the patients with STS other than GIST assessed by FDG-PET achieved metabolic PR on continuous daily dosing of sunitinib 37.5 mg. Early metabolic response did not appear to correlate with RECIST-defined response. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Infinity, Novartis, Pfizer Inc Novartis, Pfizer Inc. Infinity, Novartis, Pfizer Inc. Infinity, Novartis, Pfizer Inc.