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.
Bibliographical notePublisher Copyright:
© 2016, Springer Science+Business Media New York.
- Breast cancer brain metastases
- MRI brain