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Pharmacodynamic study using FLT PET/CT in patients treated with axitinib
Abstract   Open access   Peer reviewed

Pharmacodynamic study using FLT PET/CT in patients treated with axitinib

Glenn Liu, Peter Scully, Jill Kolesar, Justine Yang Bruce, Jens C. Eickhoff, Scott Perlman, Lakeesha Carmichael, Jennifer Heideman and Robert Jeraj
Journal of clinical oncology, Vol.31(15_suppl), pp.2537-2537
05/20/2013
DOI: 10.1200/jco.2013.31.15_suppl.2537
url
https://doi.org/10.1200/jco.2013.31.15_suppl.2537View
Published (Version of record) Open Access

Abstract

Abstract only 2537 Background: Axitinib (AX) is a potent VEGFR2 TKI. The objective of this study was to characterize tumor vascular and proliferative changes in patients treated with AX. Methods: Thirty pts with solid malignancies with at least one target lesion appropriate for FLT PET/CT imaging were enrolled. Pts were treated in Cycle #1 (C1) with AX at 5 mg BID x 2 wks, followed by a 1 wk drug holiday. Subsequent cycles continued the AX BID on a continuous basis until progression or unacceptable toxicity. In cohort A, FLT PET/CT was obtained at baseline, C1D14 (during AX) and C1D21 (AX withdrawal). Cohort B used the same treatment schedule, but FLT PET/CT was obtained on C1D14, C1D16 and C1D21. At each imaging time, peak FLT Standardized Uptake Values (SUV peak ), AX pharmacokinetics and plasma VEGF levels were obtained. Results: Of the 30 total pts, 28 had at least 1 PET/CT scan with 24 completing all planned PET/CT scans (13 in Cohort A; 11 in Cohort B). Strong proliferative flare (36% increase in SUV peak from C1D14 to C1D21) was observed in majority of pts with most of the flare occurred within two days after AX withdrawal (25% increase in SUV peak from C1D14 by C1D16). A robust vascular flare paralleled proliferative flare (R=0.57). A trend linking short progression free survival with high withdrawal flare was seen (44% increase in SUV peak for PFS ≤ 6mo vs 11% increase in SUV peak for PFS > 6 mo; p=0.14). VEGF levels and AX PK levels increased during treatment, followed by decrease during withdrawal. Conclusions: The observed AX pharmacodynamics is consistent with our prior observation with another VEGFR TKI and suggests that acute AX withdrawal results in a robust withdrawal flare. This information suggests that the timing of cytotoxic chemotherapy during the flare may increase the therapeutic index, as opposed to concurrent administration which may be antagonistic. This study also shows the power of quantitative molecular imaging, which can simultaneous evaluate treatment response heterogeneity, as well as compensatory effects that may lead to early treatment failure. Clinical trial information: NCT00859118.

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