American Association for Cancer Research
10780432ccr140491-sup-127440_1_supp_2458671_n541s5.doc (90 kB)

Supplementary Figure 1, Tables 1 - 4 from 89Zr-trastuzumab and 89Zr-bevacizumab PET to Evaluate the Effect of the HSP90 Inhibitor NVP-AUY922 in Metastatic Breast Cancer Patients

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posted on 2023-03-31, 19:09 authored by Sietske B.M. Gaykema, Carolien P. Schröder, Joanna Vitfell-Rasmussen, Sue Chua, Thijs H. Oude Munnink, Adrienne H. Brouwers, Alfons H.H. Bongaerts, Mikhail Akimov, Cristina Fernandez-Ibarra, Marjolijn N. Lub-de Hooge, Elisabeth G.E. de Vries, Charles Swanton, Udai Banerji

Supplementary Figure 1. The arithmetic mean concentration-time profiles for AUY922 and BJP762. Supplementary Table 1. The most common adverse events of AUY922. Supplementary Table 2. Adverse events with CTCAE grades 3 and 4. Supplementary Table 3. The SUVmax of 89Zr-trastuzumab before and during treatment with AUY922. Supplementary Table 4. SUVmax of 89Zr-bevacizumab before and during treatment with AUY922.



Purpose: HSP90 chaperones have key client proteins that are involved in all hallmarks of breast cancer growth and progression. The primary aim of this clinical trial was to evaluate the feasibility of using 89Zr-trastuzumab PET (for HER2-positive breast cancer) or 89Zr-bevacizumab PET [for estrogen receptor (ER)–positive breast cancer] to determine in vivo degradation of client proteins caused by the novel HSP90 inhibitor NVP-AUY922.Experimental Design: Of note, 70 mg/m2 NVP-AUY922 was administered intravenously in a weekly schedule to patients with advanced HER2 or ER-positive breast cancer. Biomarker analysis consisted of serial PET imaging with 2[18F]fluoro-2-deoxy-D-glucose (FDG), 89Zr-trastuzumab, or 89Zr-bevacizumab. Response evaluation was performed according to RECIST1.0. FDG, 89Zr-trastuzumab, and 89Zr-bevacizumab distributions were scored visually and quantitatively by calculating the maximum standardized uptake values (SUVmax). In blood samples, serial HSP70 levels, extracellular form of HER2 (HER2-ECD), and pharmacokinetic and pharmacodynamic parameters were measured.Results: Sixteen patients (ten HER2-positive and six ER-positive tumors) were included. One partial response was observed; seven patients showed stable disease. SUVmax change in individual tumor lesions on baseline versus 3 weeks 89Zr-trastuzumab PET was heterogeneous and related to size change on CT after 8 weeks treatment (r2 = 0.69; P = 0.006). Tumor response on 89Zr-bevacizumab PET and FDG-PET was not correlated with CT response.Conclusions: NVP-AUY922 showed proof-of-concept clinical response in HER2-amplified metastatic breast cancer. Early change on 89Zr-trastuzumab PET was positively associated with change in size of individual lesions assessed by CT. Clin Cancer Res; 20(15); 3945–54. ©2014 AACR.

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