ANG1005 for breast cancer brain metastases: correlation between 18 F-FLT–PET after first cycle and MRI in response assessment
Breast Cancer Research and Treatment(2016)
摘要
Purpose 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 18 F-FLT–PET for response assessment. Methods Ten patients with measurable BCBM received ANG1005 at a dose of 550 mg/m 2 IV every 21 days. Before and after cycle 1, patients underwent PET imaging with 18 F-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. Results 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 SUV max was −20.9 % ( n = 29 lesions; lower, upper quartiles: −42.4, 2.0 %), and the median percentage change in SUV 80 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. Conclusions ANG1005 warrants further study in BCBM. Results demonstrated a moderately strong association between MRI and 18 F-FLT–PET imaging.
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关键词
Breast cancer brain metastases,ANG1005,18F-FLT–PET,MRI brain
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