Entry Detail
| General information | |
| Database: | DB00370 |
| Objective: | No effective standard treatment exists for patients with radioiodinerefractory, advanced differentiated thyroid carcinoma. They aimed to assess efficacy and safety of vandetanib, a tyrosine kinase inhibitor of RET, VEGFR and EGFR signalling, in this setting. |
| Authors: | Leboulleux S, et al |
| Title: | Vandetanib in locally advanced or metastatic differentiated thyroid cancer: a randomised, doubleblind, phase 2 trial. |
| Journal: | Lancet Oncol. |
| Year: | 2012 |
| PMID: | 22898678 |
| Trial Design | |
| Clinical Trial Id: | NCT00537095 |
| Agent: | vandetanib |
| Target: | Epidermal growth factor receptor Vascular endothelial growth factor receptor 2 Protooncogene tyrosineprotein kinase receptor ret |
| Cancer Type: | thyroid cancer |
| Cancer Subtype: | advacned thyroid carcinoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | randomised, doubleblind, placebocontrolledphase II study |
| Key Patients Feature: | they enrolled patients aged 18 years or olderwith histologically confirmed locally advanced (surgicallyunresectable) or metastatic differentiated thyroidcarcinoma (papillary, follicular, or poorly differentiated, without an anaplastic component). Poorly differentiatedthyroid cancer was classified according to the Turindiagnostic criteria.17 they required an archived tissuesample for central histological review. All patients hadtarget lesions according to Response Evaluation Criteriain Solid Tumors (RECIST) version 1.018 and wereunsuitable for radioiodine therapy because of progression after previous radioiodine treatment or had oneor more lesion without detectable radioiodine uptake.Eligible patients had serum thyroidstimulating hormoneconcentrations of less than the normal reference range(<0.5 mIU/L); a WHO performance status of 2 or less;normal cardiac, haematological, hepatic, and renalfunction; and a life expectancy of 12 weeks or more.Patients with brain metastases were eligible if theirtreatment had stopped 4 weeks or more before the date ofrandomisation and had remained stable without steroidsfor 10 days or more. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | A:vandetanib ) B: matched placebo |
| Treatment Info: | Eligible patients were sequentially randomised in a 1:1 ratio with a standard computerised scheme to receive either vandetanib 300 mg per day (vandetanib group) or matched placebo (placebo group), balanced by centre. |
| Primary End Point: | progression free survival (PFS) |
| Secondary End Point: | NA |
| Patients Number: | 145 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | 41 (57%) of 72 patients in the vandetanib group and 31 (42%) of 73 in the placebo group |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 11.1 months (95% CI 7.7-14.0) for patients in the vandetanib group and 5.9 months (4.0-8.9) for patients in the placebo group. |
| Median OS A vs. C: | NR(not reached) |
| Adverse Event(agent arm): | The most common grade 3 or worse adverse events were QTc prolongation (ten [14%] of 73 patients in the vandetanib group vs none in the placebo group), diarrhoea (seven [10%] vs none), asthenia (fi ve [7%] vs three [4%]), and fatigue (four [5%] vs none). Two patients in the vandetanib group and one in the placebo group died from treatmentrelated serious adverse events (haemorrhage from skin metastases and pneumonia in the vandetanib group and pneumonia in the placebo group). |
| Conclusions: | Vandetanib is the first targeted drug to show evidence of efficacy in a randomisedphase 2 trial in patients with locally advanced or metastatic differentiated thyroid carcinoma. Further investigation of tyrosinekinase inhibitors in this setting is warranted. |