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Michael B. Bass, Steven I. Sherman, Martn J. Schlumberger, Michael T. Davis, Lisa Kivman, Huan-Mei Khoo, Kimberly H. Notari, Matthew Peach, Yong-jiang Hei, Scott D. Patterson, Biomarkers as Predictors of Response to Treatment with Motesanib in Patients with Progressive Advanced Thyroid Cancer, The Journal of Clinical Endocrinology & Metabolism, Volume 95, Issue 11, 1 November 2010, Pages 5018–5027, https://doi.org/10.1210/jc.2010-0947
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Context: Antiangiogenic therapies have shown potential in the treatment of advanced thyroid cancer, but it is uncertain which patients are most likely to benefit from therapy.
Objective: This prespecified exploratory analysis investigated whether baseline levels and/or changes in circulating biomarkers could predict tumor response and/or progression-free survival (PFS) among patients enrolled in a phase 2 study of motesanib in advanced thyroid cancer.
Design/Setting/Patients: Patients with progressive locally advanced or metastatic medullary or differentiated thyroid cancer received motesanib 125 mg once daily for up to 48 wk in a phase 2 interventional study. Samples for assessment of circulating biomarkers of angiogenesis or apoptosis were collected at study wk 1 (baseline), 2, 4, 8, 16, 24, 32, 40, 48, and 4 wk after cessation of motesanib treatment. Tumor response was assessed per Response Evaluation Criteria in Solid Tumors by independent review.
Results: Change from baseline in serum placental growth factor (PlGF) after 1 wk of treatment correlated with best tumor response (Kendall rank correlation, 0.28; P < 0.0001). Using a Fisher exact test, the most significant separation between patients who had an objective response and those who did not was at a 4.7-fold increase in PlGF. The response rate among patients with a greater than 4.7-fold increase in PlGF was 30% compared with 3% below this threshold. There was also a significant separation between responders and nonresponders at a 1.6-fold decrease in soluble vascular endothelial growth factor (VEGF) receptor 2 after 3 wk of treatment. Patients with baseline serum VEGF less than 671 pg/ml had significantly longer PFS times than the remainder of patients.
Conclusions: Changes in PlGF and soluble VEGF receptor 2 levels after initiation of therapy predicted response to motesanib in patients with advanced differentiated thyroid cancer or metastatic medullary thyroid cancer. Lower baseline VEGF levels were associated with longer PFS.
