Placental growth factor as a marker of therapeutic response to treatment with motesanib in patients with progressive advanced thyroid cancer, advanced nonsquamous non-small cell lung cancer, and locally recurrent or advanced metastatic breast cancer. (2010)

3037^ Background: We evaluated the effects of motesanib, an orally administered small-molecule antagonist of VEGF receptors 1, 2, and 3; PDGFR; and Kit, on angiogenic biomarkers among patients enrolled in three phase II studies and assessed associations between biomarker changes and outcomes. Methods: Blood samples were collected from baseline (pretreatment) until 30 days after the last treatment in 178 patients with differentiated or medullary thyroid cancer (TC) who received motesanib 125 mg QD; 143 patients with non-small cell lung cancer (NSCLC) who received carboplatin/paclitaxel plus motesanib 125 mg QD, motesanib 75 mg BID (5 d on/2 d off), or bevacizumab 10 mg/kg Q3W; and 224 patients with metastatic breast cancer (MBC) who received paclitaxel plus placebo, motesanib 125 mg QD, or bevacizumab 10 mg/kg Q2W. Five serum biomarkers were measured by multiplexed immunoassays. Associations between biomarkers and objective response (per RECIST) were assessed using Fisher exact tests. Results: Of the tested biomarkers, only placental growth factor (PlGF) elevation appeared to predict clinical outcome across tumor types. In each study, PlGF increased from baseline during treatment with motesanib (maximal increase, 2.5- to 3.7-fold). PlGF increased during bevacizumab treatment (NSCLC, 1.5-fold; MBC, 1.7-fold). TC patients who had a >5.3-fold change in PlGF after 3 weeks were more likely to have an objective response than patients who did not (41% vs 3%; p<0.0001). Nineteen percent of patients had a >5.3-fold change in PlGF from baseline. Similar (but not statistically significant) associations were observed in NSCLC (p=0.051) and MBC patients (p=0.057) who received motesanib 125 mg QD. PlGF levels were not associated with response in patients who received bevacizumab. Conclusions: A growing body of evidence supports PlGF as a marker of therapeutic response that predicts clinical outcomes of treatment with motesanib in patients with TC, NSCLC, and MBC. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, Genomic Health, sanofi-aventis Amgen, Genomic Health, sanofi-aventis 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.