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.

• Authors: C C O'Sullivan, M Lindenberg, C Bryla, N Patronas, C J Peer, L Amiri-Kordestani, N Davarpanah, E M Gonzalez, M Burotto, P Choyke, S M Steinberg, D J Liewehr, W D Figg, T Fojo, S Balasubramaniam, S E Bates
• Journal: Breast cancer research and treatment (Breast Cancer Res Treat) Vol. 160 Issue 1 Pg. 51-59 (11 2016) ISSN: 1573-7217 [Electronic] Netherlands
• PMID: 27620882 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Biomarkers
• Biomarkers, Tumor
• Peptides
• paclitaxel-Angiopep-2 conjugate
• Fluorodeoxyglucose F18
• Paclitaxel

Topics

• Adult
• Antineoplastic Agents (administration & dosage, adverse effects, therapeutic use)
• Biomarkers
• Biomarkers, Tumor
• Brain Neoplasms (diagnosis, drug therapy, secondary)
• Breast Neoplasms (diagnosis, metabolism, pathology)
• Combined Modality Therapy
• Female
• Fluorodeoxyglucose F18
• Humans
• Immunohistochemistry
• In Situ Hybridization, Fluorescence
• Magnetic Resonance Imaging
• Middle Aged
• Paclitaxel (administration & dosage, adverse effects, analogs & derivatives, therapeutic use)
• Peptides (administration & dosage, adverse effects, therapeutic use)
• Positron-Emission Tomography
• Treatment Outcome