Biomarkers as potential predictors of response to treatment with motesanib or bevacizumab in combination with paclitaxel (P) in patients (pts) with locally recurrent or advanced metastatic breast cancer (MBC).
Authors: S. D. Patterson, M. T. Davis, J. R. Mackey, M. Martin, Y. Hei, M. B. Bass
Journal: Journal of Clinical Oncology (2010)

1048^ Background: Motesanib is an orally administered small-molecule antagonist of VEGF receptors (VEGFRs) 1, 2, and 3; PDGFR; and Kit. In a phase II study, objective response rates (per RECIST) of 35%, 48%, and 45% were observed in pts with HER2-negative MBC who received first-line P plus placebo (arm A), motesanib 125 mg once daily (arm B), or bevacizumab 10 mg/kg every 2 weeks (arm C; Eur J Cancer Suppl. 2009; 7[2]:259). We evaluated whether pharmacodynamic changes in angiogenic biomarkers are associated with tumor response. Methods: Blood samples were collected from baseline (pretreatment) until 30 days after study completion. Serum samples from 224 of 277 treated pts were available for analysis. A panel of 5 biomarkers was measured by electrochemiluminescent multiplexed sandwich immunoassays. Analyses were performed using the Fisher exact test on log-transformed values. Results: In both arms B and C placental growth factor (PlGF) showed the greatest change from baseline (arm B, 3.69-fold increase after 3 wks, p<.001; arm C, 1.65-fold increase after 3 wks, p<.001). Change in PlGF predicted response in arm B but not in arm C; best separation between pts with and without responses was at a 2.0-fold change in PlGF after 3 wks (p=.057; n=44). The response rate was 65% above this threshold and 30% below it. Other biomarkers responded differently to bevacizumab and motesanib treatment. In arm B, soluble VEGFR2 (sVEGFR2) and sKit decreased (maximal decrease, 1.64-fold, p<.001; and 1.35-fold, p<0.001, respectively) while VEGF increased (1.47-fold, p=0.003) from baseline. Levels of sVEGFR1 were unchanged. In arm C, small changes in sVEGFR2 above and below baseline were observed while sKit remained unchanged. Treatment with P (arm A) had little effect on biomarker concentrations, suggesting that the changes in arms B and C were specific to motesanib and bevacizumab. Conclusions: Differences in the response of angiogenic biomarkers to treatment with motesanib or bevacizumab were observed. Changes in circulating PlGF are associated with subsequent tumor response to treatment with P plus motesanib in pts with HER2-negative MBC. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen Amgen In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519-521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2010 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest.