ANG1005 for breast cancer brain metastases: correlation between18F-FLT-PET after first cycle and MRI in response assessment.
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 evaluate18F-FLT-PET for response assessment.



Ten patients with measurable BCBM received ANG1005 at a dose of 550 mg/m2IV every 21 days. Before and after cycle 1, patients underwent PET imaging with18F-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 SUVmaxwas -20.9 % (n = 29 lesions; lower, upper quartiles: -42.4, 2.0 %), and the median percentage change in SUV80was 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 and18F-FLT-PET imaging.
National Cancer Institute, Bethesda, MD, USA. osullivan.ciara@mayo.edu.|Department of Medical Oncology, Mayo Clinic, 200 1st Street SW, Rochester, MN, 55905, USA. osullivan.ciara@mayo.edu.
C C
CC
O'Sullivan
National Cancer Institute, Bethesda, MD, USA.
M
M
Lindenberg
National Cancer Institute, Bethesda, MD, USA.
C
C
Bryla
National Cancer Institute, Bethesda, MD, USA.
N
N
Patronas
National Cancer Institute, Bethesda, MD, USA.
C J
CJ
Peer
National Cancer Institute, Bethesda, MD, USA.
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L
Amiri-Kordestani
National Cancer Institute, Bethesda, MD, USA.
N
N
Davarpanah
National Cancer Institute, Bethesda, MD, USA.
E M
EM
Gonzalez
National Cancer Institute, Bethesda, MD, USA.|Pontificia Universidad Católica de Chile, Santiago, Chile.
M
M
Burotto
National Cancer Institute, Bethesda, MD, USA.
P
P
Choyke
National Cancer Institute, Bethesda, MD, USA.
S M
SM
Steinberg
National Cancer Institute, Bethesda, MD, USA.
D J
DJ
Liewehr
National Cancer Institute, Bethesda, MD, USA.
W D
WD
Figg
National Cancer Institute, Bethesda, MD, USA.|Columbia University, New York, NY, USA.
T
T
Fojo
National Cancer Institute, Bethesda, MD, USA.
S
S
Balasubramaniam
National Cancer Institute, Bethesda, MD, USA.|Columbia University, New York, NY, USA.
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Bates
D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers; D014408:Biomarkers, Tumor; D001932:Brain Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000556:secondary*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology*; D003131:Combined Modality Therapy; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010455:Peptides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D049268:Positron-Emission Tomography; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D015415:Biomarkers; D014408:Biomarkers, Tumor; D010455:Peptides; C531859:paclitaxel-Angiopep-2 conjugate; D019788:Fluorodeoxyglucose F18; D017239:Paclitaxel
18F-FLT–PET; ANG1005; Breast cancer brain metastases; MRI brain