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


ABSTRACT: 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 18F-FLT-PET for response assessment. METHODS:Ten patients with measurable BCBM received ANG1005 at a dose of 550 mg/m2 IV every 21 days. 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. 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 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. CONCLUSIONS:ANG1005 warrants further study in BCBM. Results demonstrated a moderately strong association between MRI and 18F-FLT-PET imaging.

SUBMITTER: O'Sullivan CC 

PROVIDER: S-EPMC6362453 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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

O'Sullivan C C CC   Lindenberg M M   Bryla C C   Patronas N N   Peer C J CJ   Amiri-Kordestani L L   Davarpanah N N   Gonzalez E M EM   Burotto M M   Choyke P P   Steinberg S M SM   Liewehr D J DJ   Figg W D WD   Fojo T T   Balasubramaniam S S   Bates S E SE  

Breast cancer research and treatment 20160912 1


<h4>Purpose</h4>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 <sup>18</sup>F-FLT-PET for response assessment.<h4>Methods</h4>Ten patients with measurable BCBM received ANG1005 at a dose of 550 mg/m<sup>2</sup> IV every 21 days. Before and after cycle 1, pati  ...[more]

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