ANG1005 for breast cancer brain metastases: correlation between 18F-FLT-PET after first cycle and MRI in response assessment.

Abstract

Improved therapies and imaging modalities are needed for the treatment of breast cancer brain metastases (BCBM). ANG1005 is a drug conjugate consisting of paclitaxel covalently linked to Angiopep-2, designed to cross the blood-brain barrier. We conducted a biomarker substudy to evaluate 18F-FLT-PET for response assessment. Ten patients with measurable BCBM received ANG1005 at a dose of 550mg/m2 IV every 21days. Before and after cycle 1, patients underwent PET imaging with 18F-FLT, a thymidine analog, retention of which reflects cellular proliferation, for comparison with gadolinium-contrast magnetic resonance imaging (Gd-MRI) in brain metastases detection and response assessment. A 20% change in uptake after one cycle of ANG1005 was deemed significant. Thirty-two target and twenty non-target metastatic brain lesions were analyzed. The median tumor reduction by MRI after cycle 1 was -17.5% (n=10 patients, lower, upper quartiles: -25.5, -4.8%) in target lesion size compared with baseline. Fifteen of twenty-nine target lesions (52%) and 12/20 nontarget lesions (60%) showed a ≥20% decrease post-therapy in FLT-PET SUV change (odds ratio 0.71, 95% CI: 0.19, 2.61). The median percentage change in SUVmax was -20.9% (n=29 lesions; lower, upper quartiles: -42.4, 2.0%), and the median percentage change in SUV80 was also -20.9% (n=29; lower, upper quartiles: -49.0, 0.0%). Two patients had confirmed partial responses by PET and MRI lasting 6 and 18 cycles, respectively. Seven patients had stable disease, receiving a median of six cycles. ANG1005 warrants further study in BCBM. Results demonstrated a moderately strong association between MRI and 18F-FLT-PET imaging.