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

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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.

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Acknowledgments

We would like to thank all the patients, their families, the research, and allied health professional staff in the National Cancer Institute for their valuable contributions to this study. ANG1005 was provided by Angiochem, and representatives from the company reviewed the manuscript. None of the authors have a financial relationship with Angiochem or have other relevant conflicts of interest to disclose.

Author contributions

Both Susan E. Bates and Antonio T. Fojo had full access to all of the data in the study and took responsibility for the integrity of the data and the accuracy of the data analysis.

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Authors and Affiliations

  1. National Cancer Institute, Bethesda, MD, USA

    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

  2. Department of Medical Oncology, Mayo Clinic, 200 1st Street SW, Rochester, MN, 55905, USA

    C. C. O’Sullivan

  3. Pontificia Universidad Católica de Chile, Santiago, Chile

    M. Burotto

  4. Columbia University, New York, NY, USA

    T. Fojo & S. E. Bates

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  1. C. C. O’Sullivan
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Correspondence to C. C. O’Sullivan.

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O’Sullivan, C.C., Lindenberg, M., Bryla, C. et al. ANG1005 for breast cancer brain metastases: correlation between 18F-FLT–PET after first cycle and MRI in response assessment. Breast Cancer Res Treat 160, 51–59 (2016). https://doi.org/10.1007/s10549-016-3972-z

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  • DOI: https://doi.org/10.1007/s10549-016-3972-z

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