By Crystal Phend, Senior Staff Writer, MedPage Todaymedullary type of thyroid cancer last year.
Other kinase inhibitors also appear promising in the differentiated type that accounts for about 90% of thyroid cancer cases.
Single-arm studies have shown “striking and durable disease regression” with partial response rates approaching 50% with drugs like sorafenib (Nexavar), sunitinib (Sutent), pazopanib (Votrient), and axitinib (Inlyta), Keith C. Bible, MD, PhD, of the Mayo Clinic in Rochester, Minn., pointed out in an accompanying editorial.
None of the trials have shown any overall survival advantage from targeted agents in thyroid cancer, he noted.
With questionable effect on overall disease trajectory, the substantial toxicity of the kinase inhibitors is a concern, Bible explained.
“This excess mortality of 1.5% in the vandetanib group is consistent with reports of similarly increased treatment-related mortality for other kinase inhibitors,” Bible wrote.
Similar to the potentially fatal problem of polymorphic ventricular tachycardia (torsades de pontes) that led to a risk evaluation and mitigation strategy (REMS) program for vandetanib in medullary thyroid cancer, the most common serious adverse event with the drug in differentiated cancers was QTc prolongation, at 14%.
Other common grade 3 or worse risks with vandetanib were diarrhea (7% versus 0% with placebo), asthenia (7% versus 4%), and fatigue (5% versus 0%), though no previously unknown safety issues were seen in the trial.
The double-blind trial included patients from across Europe with surgically unresectable locally advanced or metastatic differentiated thyroid cancer, whether papillary, follicular, or poorly differentiated without an anaplastic component.
Placebo-group patients could cross over to open-label vandetanib at the 300 mg dose used in the trial after objective disease progression or 12 months of stable disease, and 81% did so, confounding any analysis of overall survival.
Overall survival data at least suggested no disadvantage to vandetanib, with an odds ratio 0.92 (P=0.80).
The odds of progression-free survival as the primary endpoint, though, did significantly favor the drug over placebo (hazard ratio 0.63, one-sided P=0.008, two-sided P=0.017).
Partial objective responses tended to be more common with vandetanib, with six (8%) versus four (5%) with placebo, for an odds ratio of 1.57, though not significant at P=0.501.
The study was funded by AstraZeneca.
Schlumberger reported having attended advisory boards and received payment for lectures for AstraZeneca, Bayer, Eisai, Exelixis, Genzyme, and Roche.
Two coauthors reported being AstraZeneca employees.
Bible reported having no conflicts of interest to disclose.
Primary source: The Lancet Oncology
Source reference:
Leboulleux S, et al “Vandetanib in locally advanced or metastatic differentiated thyroid cancer: A randomised, double-blind, phase 2 trial” Lancet Oncol 2012; DOI: 10.1016/S1470-2045(12)70335-2.
Additional source: The Lancet Oncology
Source reference:
Bible KC “Treating advanced radioresistant differentiated thyroid cancer” Lancet Oncol 2012; DOI: 10.1016/S1470-2045(12)70342-X.
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Crystal Phend
Staff Writer
Crystal Phend joined MedPage Today in 2006 after roaming conference halls for publications including The Medical Post, Oncology Times, Doctor's Guide, and the journal IDrugs. When not covering medical meetings, she writes from Silicon Valley, just south of the San Francisco fog.
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