Vandetanib Prolongs PFS in Locally Advanced, Metastatic Differentiated Thyroid Cancer

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(ChemotherapyAdvisor) – The first targeted agent to prolong progression-free survival (PFS) in a randomized phase 2 trial in patients with locally advanced or metastatic differentiated thyroid carcinoma (DTC) is vandetanib, a tyrosine kinase inhibitor of RET, VEGFR and EGFR signaling, results published in The Lancet Oncology online August 14 have found.

The study, conducted in 7 European countries, randomly assigned 145 patients with locally advanced or metastatic papillary, follicular, or poorly differentiated DTC failing or unsuitable for radioiodine therapy to oral vandetanib 300mg/day (n=72) or placebo (n=73) between September 2007 and October 2008, noted Martin Schlumberger, MD, from the Institut Gustave Roussy in France and colleagues.

At data cut-off in December 2009, 52 patients (72%) in the vandetanib group and 61 (84%) in the placebo group had disease progression. Median PFS was 11.1 months (95% CI 7.7–14.0) for patients in the vandetanib arm and 5.9 months (4.0–8.9) for those in the placebo arm (HR 0.63; 60% CI 0.54–0.74; one-sided P=0.008). Patients with papillary DTC had a median PFS of 16.2 months vs 7.7 months for those with either follicular or poorly differentiated disease.

Objective responses—all partial—were noted by the investigators in 6 of 72 patients (8%) in the vandetanib group and 4 of 73 (5%) in the placebo group (OR 1.57; 95% CI 0.42–5.81; P=0.501).

The most common grade 3 or worse adverse events were QTc prolongation (14% in the vandetanib group vs 0% in the placebo group), diarrhea (10% vs 0%), asthenia (7% vs 4%), and fatigue (5% vs 0%). Two treatment-related deaths occurred in the vandetanib group (hemorrhage from skin metastases and pneumonia) vs 1 (pneumonia) in the placebo group.

“These results are potentially good news for patients with aggressive DTC who currently have few treatment options,” Dr. Schlumberger said. In a linked Comment, Keith C. Bible, MD, PhD, Mayo Clinic, Rochester, USA wrote, “Despite providing important additional evidence about the clinical activity of vandetanib in DTC, [the study] leaves the important issue of the effect of vandetanib on overall survival unresolved.” He adds, “More work is needed to better clarify which patients with DTC might have the greatest net benefits from kinase inhibitors…and to develop individualized treatment approaches in DTC.”

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