Analysis of Biomarkers and Association With Clinical Outcomes in Patients With Differentiated Thyroid Cancer: Subanalysis of the Sorafenib Phase III DECISION Trial
The phase III DECISION trial (NCT00984282; EudraCT:2009-012007-25) established sorafenib efficacy in locally recurrent or metastatic, progressive, differentiated thyroid cancer (DTC) refractory to radioactive iodine. We conducted a retrospective, exploratory biomarker analysis of patients from DECIS...
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| Published in: | Clinical cancer research Vol. 25; no. 24; pp. 7370 - 7380 |
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| Main Authors: | , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
United States
15-12-2019
|
| Online Access: | Get full text |
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| Summary: | The phase III DECISION trial (NCT00984282; EudraCT:2009-012007-25) established sorafenib efficacy in locally recurrent or metastatic, progressive, differentiated thyroid cancer (DTC) refractory to radioactive iodine. We conducted a retrospective, exploratory biomarker analysis of patients from DECISION.
Candidate biomarkers [15 baseline plasma proteins, baseline and during-treatment serum thyroglobulin, and relevant tumor mutations (
,
,
, and
)] were analyzed for correlation with clinical outcomes.
Plasma biomarker and thyroglobulin data were available for 395 of 417 (94.7%) and 403 of 417 (96.6%) patients, respectively. Elevated baseline VEGFA was independently associated with poor prognosis for progression-free survival [PFS; HR = 1.82; 95% confidence interval (CI), 1.38-2.44;
= 0.0007], overall survival (HR = 2.13; 95% CI, 1.37-3.36;
= 0.013), and disease-control rate (DCR; OR = 0.30;
= 0.009). Elevated baseline thyroglobulin was independently associated with poor PFS (HR = 2.03; 95% CI, 1.52-2.71;
< 0.0001) and DCR (OR = 0.32;
= 0.01). Combined VEGFA/thyroglobulin signatures correlated with poor PFS (HR = 2.12; 95% CI, 1.57-2.87;
< 0.00001). Thyroglobulin decrease ≥30% from baseline was achieved by 76% and 14% of patients receiving sorafenib and placebo, respectively (
< 0.001). Patients with ≥30% thyroglobulin reduction had longer PFS than those without ≥30% reduction [HR (95% CI): sorafenib = 0.61 (0.40-0.94),
= 0.022; placebo = 0.49 (0.29-0.85),
= 0.009].
mutations were associated with better PFS;
mutations were associated with worse PFS, although neither was independently prognostic in multivariate models. No examined biomarker predicted sorafenib benefit.
We identified biomarkers associated with poor prognosis in DTC, including elevated baseline VEGFA and thyroglobulin and the presence of
mutations. Serum thyroglobulin may be a biomarker of tumor response and progression. |
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| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 ObjectType-News-3 content type line 23 |
| ISSN: | 1078-0432 1557-3265 |
| DOI: | 10.1158/1078-0432.CCR-18-3439 |