Early response evaluation of therapy with AP23573 (an mTOR inhibitor) in sarcoma using [18F]2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) scan

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9028 Background: AP23573 (AP) is a non-prodrug rapamycin analog, which potently inhibits mTOR, a downstream effector of the PI3K/Akt pathway. AP has demonstrated some anti-tumor efficacy in sarcoma in phase I study. The relationship between mTOR and the glycolytic pathway provides mechanistic rationale for the use of PET as a non-invasive indicator of mTOR activity. Early response evaluation by PET was studied in this phase 2 trial in advanced sarcoma pts. Methods: AP is dosed at 12.5 mg IV daily X 5 days every 2 weeks (1 course). PET scan was done on D1 and D5 of the first course of AP using a CTI Viewer 16 PET/CT scanner with LSO crystals (11 pts) or a Siemens Biograph 2 PET/CT scanner with LSO crystals (14 pts). The five areas with highest FDG accumulation at baseline were selected as target lesions. Percent difference in sum of maximum standard uptake values (SUVmax) were compared for each patient on D1 and D5. These values represent a measure of FDG uptake. Response criteria used were recommended by the EORTC PET Study Group (Eur J Cancer. 1999; 35; 1773–1782). In the targeted lesions D5, SUVmax normalization was considered as complete metabolic response (CMR), while >25% SUVmax reduction was considered partial metabolic response (PMR). Stable metabolic response (SMR) was defined by an SUVmax change less then ±25% and increased metabolic response (IMR) was considered >25% increase in SUVmax. Further evaluation with PET scan is planned after 4 courses of AP. Results: 25 pts (14M/11F) were enrolled (age 18–76 yrs, median 57 yrs). Two pts showed no abnormal 18-FDG accumulation on D1, hence D5 PET was omitted. Of the remaining 23 pts, 9 pts (39%) showed PMR (SUV decreased by 25.3–58.7%). 14 pts (61%) had SMR (9 pts had SUV decrease by 4.7–21.6% and 5 pts had SUV increase by 0.7–5.5%). None of the patients had IMR or CMR. 5/9 pts with PET evidence of PMR showed clinical improvement as demonstrated by reduced symptoms of pain, shortness of breath and cough. Conclusions: This is the first known report of the use of PET to evaluate mTOR inhibition in non-GIST sarcomas. PET appears to be valuable in initial evaluation of patient response to treatment with AP. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ariad Ariad Ariad