Biomarkers as predictors of response to treatment with motesanib in patients with progressive advanced thyroid cancer.

Abstract

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.

• Authors: Michael B Bass, Steven I Sherman, Martin J Schlumberger, Martn J Schlumberger, Michael T Davis, Lisa Kivman, Huan-Mei Khoo, Kimberly H Notari, Matthew Peach, Yong-Jiang Hei, Scott D Patterson
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 95 Issue 11 Pg. 5018-27 (Nov 2010) ISSN: 1945-7197 [Electronic] United States
• PMID: 20739388 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Biomarkers
• Indoles
• Oligonucleotides
• PGF protein, human
• Pregnancy Proteins
• Vascular Endothelial Growth Factor A
• Placenta Growth Factor
• Niacinamide
• Vascular Endothelial Growth Factor Receptor-2
• imetelstat

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (therapeutic use)
• Biomarkers (blood)
• Carcinoma, Medullary (blood, drug therapy, pathology)
• Disease-Free Survival
• Enzyme-Linked Immunosorbent Assay
• Female
• Humans
• Indoles (therapeutic use)
• Male
• Middle Aged
• Niacinamide (analogs & derivatives, therapeutic use)
• Oligonucleotides
• Placenta Growth Factor
• Pregnancy Proteins (blood)
• Thyroid Neoplasms (blood, drug therapy, pathology)
• Treatment Outcome
• Vascular Endothelial Growth Factor A (blood)
• Vascular Endothelial Growth Factor Receptor-2 (blood)