• Head & Neck Cancers
• Thyroid Disorders Clinical Trials

• Head & Neck Cancers
• Thyroid Disorders
• Oncology Clinical Trials
• Oncology

The multitargeted agent sorafenib is the first therapy that has shown promise in a Phase 3 trial to extend progression-free survival (PFS) in patients with metastatic differentiated thyroid cancer that is refractory to standard radioactive iodine (RAI) therapy.

Interim results from a double-blind, placebo-controlled randomized Phase 3 Study of Sorafenib in Locally Advanced or Metastatic Patients With Radioactive Iodine Refractory Thyroid Cancer [DECISION; NCT00984282; Brose MS et al. J Clin Oncol 2013 (suppl; abstr 4)], for the treatment of patients with RAI refractory differentiated thyroid cancer were presented by Marcia S. Brose, MD, PhD, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Differentiated thyroid cancer accounts for the majority of the >60,000 thyroid cancer cases diagnosed each year in the United States [Howlader N et al. SEER Cancer Statistics Review. http://seer.cancer.gov/statfacts/html/thyro.html. Accessed June 2013]. Although cure rates of differentiated thyroid cancer are generally high following standard treatment with surgery and RAI, the disease becomes refractory to RAI in ∼15% of patients [Pacini F et al. Expert Rev Endocrinol Metab 2012; Xing M et al. Lancet 2013]. Their median survival after resistance develops is 2.5 to 3.5 years, and bone, pulmonary, and brain complications occur frequently [Durante C et al. J Clin Endocrinol Metab 2006; Robbins RJ et al. J Clin Endocrinol Metab 2006]. There is no standard therapy for patients with RAI-refractory differentiated thyroid cancer, with palliative care being the main option.

Sorafenib is a multikinase inhibitor with activity against RAF kinase and several receptor tyrosine kinases, including vascular endothelial growth factor receptor 1 to 3, platelet-derived growth factor receptors, BRAF, RET, and c-KIT.

In DECISION, 417 patients with locally advanced or metastatic, RAI-resistant differentiated thyroid cancer whose disease had progressed within the preceding 14 months (as defined by RECIST 1.0 criteria) were randomly assigned in a 1:1 ratio to receive sorafenib 400 mg orally BID or placebo. Allowance was made for crossover from placebo to sorafenib upon disease progression. The study was conducted in 89 centers across North America, Europe, and Asia.

The median PFS by independent central review, the primary endpoint, was 10.8 months in the sorafenib group versus 5.8 months in the placebo arm (HR, 0.587; p<0.0001). The benefit with sorafenib on PFS was consistent across subgroups examined. At disease progression, 150 patients assigned to placebo (71%) and 55 assigned to sorafenib (27%) received open-label sorafenib. The median overall survival has not been reached in either group.

The response rates were 12.2% and 0.5% in the sorafenib and placebo arms, respectively (p<0.0001). All were partial responses; no complete responses were observed.

Dose modification due to adverse events (AEs) was necessary in 77.8% of the sorafenib arm and 30.1% of the placebo arm. Discontinuation due to AEs occurred in 18.8% of sorafenib-treated patients versus 3.8% of the placebo group. Tolerability was consistent with the known sorafenib safety profile. The most common any-grade treatment-emergent AEs in the sorafenib arm were hand-foot skin reaction, diarrhea, alopecia, rash/desquamation, fatigue, weight loss, and hypertension. There was one death in each arm that was attributed to the study drug.

Sorafenib significantly improved PFS and extended median PFS by 5 months compared with placebo in RAI-refractory differentiated thyroid cancer, representing the first effective agent in this a rare cancer with poor prognosis and no established treatment to date.

• © 2013 MD Conference Express®