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Modulation of Circulating Protein Biomarkers in Cancer Patients Receiving Bevacizumab and the Anti-Endoglin Antibody, TRC105.

Publication ,  Journal Article
Liu, Y; Starr, MD; Brady, JC; Rushing, C; Pang, H; Adams, B; Alvarez, D; Theuer, CP; Hurwitz, HI; Nixon, AB
Published in: Mol Cancer Ther
October 2018

TRC105 is an anti-endoglin antibody currently being tested in combination with VEGF inhibitors. In the phase Ib trial, 38 patients were treated with both TRC105 and bevacizumab (BEV), and improved clinical outcomes were observed, despite the fact that 30 patients (79%) were refractory to prior anti-VEGF therapy. Plasma samples were tested for angiogenic and inflammatory biomarkers at baseline and on-treatment. To provide broader context of this combination biomarker study, direct cross-study comparisons were made to biomarker studies previously conducted in patients treated with either BEV or TRC105 monotherapy. Upon treatment with BEV and TRC105, pharmacodynamic changes in response to both BEV (PlGF increase) and TRC105 (soluble endoglin increase) were noted. In addition, distinct patterns of change were identified (similar, opposing, neutralizing). Similar patterns were observed when the combination elicited similar effects to those observed with monotherapy treatment (i.e., decreases of Ang-2, increases of IL6 and VCAM-1). Opposing patterns were observed when the combination led to opposing effects compared with monotherapy treatment (i.e., TGFβ1, PDGF-AA and PDGF-BB, PAI-1). Lastly, neutralizing patterns were observed when one drug led to increase, whereas the other drug led to decrease, and the combination elicited no overall effect on the marker (i.e., VEGF-A, VEGF-D, and IGFBP-3). Patients achieving partial responses or stable disease from the combination exhibited significantly lower expression of E-Cadherin, HGF, ICAM-1, and TSP-2 at baseline. Taken together, the novel biomarker modulations identified may deepen our understanding of the underlying biology in patients treated with BEV and TRC105 compared with either drug alone. Mol Cancer Ther; 17(10); 2248-56. ©2018 AACR.

Duke Scholars

Published In

Mol Cancer Ther

DOI

EISSN

1538-8514

Publication Date

October 2018

Volume

17

Issue

10

Start / End Page

2248 / 2256

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Oncology & Carcinogenesis
  • Neoplasms
  • Male
  • Humans
  • Female
  • Endoglin
  • Biomarkers, Tumor
  • Bevacizumab
  • Antineoplastic Agents, Immunological
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Liu, Y., Starr, M. D., Brady, J. C., Rushing, C., Pang, H., Adams, B., … Nixon, A. B. (2018). Modulation of Circulating Protein Biomarkers in Cancer Patients Receiving Bevacizumab and the Anti-Endoglin Antibody, TRC105. Mol Cancer Ther, 17(10), 2248–2256. https://doi.org/10.1158/1535-7163.MCT-17-0916
Liu, Yingmiao, Mark D. Starr, John C. Brady, Christel Rushing, Herbert Pang, Bonne Adams, Delia Alvarez, Charles P. Theuer, Herbert I. Hurwitz, and Andrew B. Nixon. “Modulation of Circulating Protein Biomarkers in Cancer Patients Receiving Bevacizumab and the Anti-Endoglin Antibody, TRC105.Mol Cancer Ther 17, no. 10 (October 2018): 2248–56. https://doi.org/10.1158/1535-7163.MCT-17-0916.
Liu Y, Starr MD, Brady JC, Rushing C, Pang H, Adams B, et al. Modulation of Circulating Protein Biomarkers in Cancer Patients Receiving Bevacizumab and the Anti-Endoglin Antibody, TRC105. Mol Cancer Ther. 2018 Oct;17(10):2248–56.
Liu, Yingmiao, et al. “Modulation of Circulating Protein Biomarkers in Cancer Patients Receiving Bevacizumab and the Anti-Endoglin Antibody, TRC105.Mol Cancer Ther, vol. 17, no. 10, Oct. 2018, pp. 2248–56. Pubmed, doi:10.1158/1535-7163.MCT-17-0916.
Liu Y, Starr MD, Brady JC, Rushing C, Pang H, Adams B, Alvarez D, Theuer CP, Hurwitz HI, Nixon AB. Modulation of Circulating Protein Biomarkers in Cancer Patients Receiving Bevacizumab and the Anti-Endoglin Antibody, TRC105. Mol Cancer Ther. 2018 Oct;17(10):2248–2256.

Published In

Mol Cancer Ther

DOI

EISSN

1538-8514

Publication Date

October 2018

Volume

17

Issue

10

Start / End Page

2248 / 2256

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Oncology & Carcinogenesis
  • Neoplasms
  • Male
  • Humans
  • Female
  • Endoglin
  • Biomarkers, Tumor
  • Bevacizumab
  • Antineoplastic Agents, Immunological