Biomarkers as Predictors of Response to Treatment with Motesanib in Patients with Progressive Advanced Thyroid Cancer

• Published in: The journal of clinical endocrinology and metabolism Vol. 95; no. 11; pp. 5018 - 5027
• Main Authors: Bass, Michael B, Sherman, Steven I, Schlumberger, Martn J, Davis, Michael T, Kivman, Lisa, Khoo, Huan-Mei, Notari, Kimberly H, Peach, Matthew, Hei, Yong-jiang, Patterson, Scott D
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01.11.2010
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Biomarkers - blood; Carcinoma, Medullary - blood; Carcinoma, Medullary - drug therapy; Carcinoma, Medullary - pathology; Disease-Free Survival; Endocrinopathies; Enzyme-Linked Immunosorbent Assay; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Humans; Indoles - therapeutic use; Male; Malignant tumors; Medical sciences; Middle Aged; Niacinamide - analogs & derivatives; Niacinamide - therapeutic use; Placenta Growth Factor; Pregnancy Proteins - blood; Thyroid Neoplasms - blood; Thyroid Neoplasms - drug therapy; Thyroid Neoplasms - pathology; Thyroid. Thyroid axis (diseases); Treatment Outcome; Vascular Endothelial Growth Factor A - blood; Vascular Endothelial Growth Factor Receptor-2 - blood; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; Endocrinopathy; Antineoplastic agent; Human; Motesanib; Obesity; Nutrition; Thyroid diseases; Nutrition disorder; Biological marker; Patient; Metabolic diseases; Malignant tumor; Thyroid cancer; Treatment; Advanced stage; Predictive factor; Endocrinology; Nutritional status; Cancer
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2010-0947

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. Among patients receiving motesanib treatment for advanced thyroid cancer, changes in the serum concentration of placental growth factor were shown to predict objective response.