This is a Phase 2 trial Safety Lead-in trial conducted in 3 cohorts of patients.
A safety lead-in study of the impact of adding the Repurposed Drugs a third agent will be conducted prior to opening enrollment into the compassionate use study. All patients enrolled in the safety lead-in study may continue long-term treatment under this protocol without interruption of dosing.

开始日期2025-03-01

申办/合作机构

Evergreen Therapeutics, Inc

100 项与 FGFR2 x RET x c-Kit x VEGFR1 x FGFR3 x FGFR1 x PDGFRα x FGFR4 x VEGFR3 x VEGFR2 相关的临床结果

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100 项与 FGFR2 x RET x c-Kit x VEGFR1 x FGFR3 x FGFR1 x PDGFRα x FGFR4 x VEGFR3 x VEGFR2 相关的转化医学

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0 项与 FGFR2 x RET x c-Kit x VEGFR1 x FGFR3 x FGFR1 x PDGFRα x FGFR4 x VEGFR3 x VEGFR2 相关的专利（医药）

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项与 FGFR2 x RET x c-Kit x VEGFR1 x FGFR3 x FGFR1 x PDGFRα x FGFR4 x VEGFR3 x VEGFR2 相关的文献（医药）

2018-06-01·Cancer1区 · 医学

Treatment-emergent hypertension and efficacy in the phase 3 Study of (E7080) lenvatinib in differentiated cancer of the thyroid (SELECT).

1区 · 医学

Article

作者: Lori J Wirth ; Makoto Tahara ; Bruce Robinson ; Sanjeev Francis ; Marcia S Brose ; Mouhammed Amir Habra ; Kate Newbold ; Naomi Kiyota ; Corina E Dutcus ; Elton Mathias ; Matthew Guo ; Steven I Sherman ; Martin Schlumberger

BACKGROUND:

Hypertension (HTN) is an established class effect of vascular endothelial growth factor receptor (VEGFR) inhibition. In the phase 3 Study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid (SELECT) trial, HTN was the most frequent adverse event of lenvatinib, an inhibitor of VEGFR1, VEGFR2, VEGFR3, fibroblast growth factor receptor 1 (FGFR1), FGFR2, FGFR3, FGFR4, platelet-derived growth factor receptor α (PDGFRα), ret proto-oncogene (RET), and stem cell factor receptor (KIT). This exploratory analysis examined treatment-emergent hypertension (TE-HTN) and its relation with lenvatinib efficacy and safety in SELECT.

METHODS:

In the multicenter, double-blind SELECT trial, 392 patients with progressive radioiodine-refractory differentiated thyroid cancer (RR-DTC) were randomized 2:1 to lenvatinib (24 mg/d on a 28-day cycle) or placebo. Survival endpoints were assessed with Kaplan-Meier estimates and log-rank tests. The influence of TE-HTN on progression-free survival (PFS) and overall survival (OS) was analyzed with univariate and multivariate Cox proportional hazards models.

RESULTS:

Overall, 73% of lenvatinib-treated patients and 15% of placebo-treated patients experienced TE-HTN. The median PFS for lenvatinib-treated patients with (n = 190) and without TE-HTN (n = 71) was 18.8 and 12.9 months, respectively (hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.39-0.88; P = .0085). For lenvatinib-treated patients, the objective response rate was 69% with TE-HTN and 56% without TE-HTN (odds ratio, 1.72; 95% CI, 0.98-3.01). The median change in tumor size for patients with and without TE-HTN was -45% and -40%, respectively (P = .2). The median OS was not reached for patients with TE-HTN; for those without TE-HTN, it was 21.7 months (HR, 0.43; 95% CI, 0.27-0.69; P = .0003).

CONCLUSIONS:

Although HTN is a clinically significant adverse event that warrants monitoring and management, TE-HTN was significantly correlated with improved outcomes in patients with RR-DTC, indicating that HTN may be predictive for lenvatinib efficacy in this population. Cancer 2018;124:2365-72. © 2018 American Cancer Society.