Details

Autor(en) / Beteiligte

• O'Sullivan, C C
• Lindenberg, M
• Bryla, C
• Patronas, N
• Peer, C J
• Amiri-Kordestani, L
• Davarpanah, N
• Gonzalez, E M
• Burotto, M
• Choyke, P
• Steinberg, S M
• Liewehr, D J
• Figg, W D
• Fojo, T
• Balasubramaniam, S
• Bates, S E

Titel

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

Ist Teil von

• Breast cancer research and treatment, 2016-11, Vol.160 (1), p.51

Ort / Verlag

Netherlands

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 F-FLT-PET for response assessment. Ten patients with measurable BCBM received ANG1005 at a dose of 550 mg/m IV every 21 days. Before and after cycle 1, patients underwent PET imaging with 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. 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 was -20.9 % (n = 29 lesions; lower, upper quartiles: -42.4, 2.0 %), and the median percentage change in SUV 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 F-FLT-PET imaging.