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Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals have announced positive data from the phase III DECISION trial investigating the use of Sorafenib ( Nexavar ) tablets in patients with locally advanced or metastatic radioactive Iodine ( RAI )-refractory differentiated thyroid cancer.
Sorafenib significantly extended progression-free survival ( PFS ) compared to placebo ( hazard ratio, HR=0.587; p less than 0.0001 ), which represents a 41% reduction in the risk of progression or death for patients who received Sorafenib compared to placebo-treated patients. The median progression-free survival was 10.8 months in Sorafenib-treated patients compared to 5.8 months in those taking placebo.
Progression-free survival as defined by RECIST 1.0 ( Response Evaluation Criteria in Solid Tumors ) was the primary endpoint of this study.

There was no statistically significant difference in overall survival between treatment arms, which was expected due to the cross-over design of the study. After progression, patients receiving placebo had the option to begin open-label Sorafenib at the discretion of the investigator; 71% of placebo patients ultimately began open-label Sorafenib during the trial. Median overall survival has not yet been reached in either arm.

Safety and tolerability in the study were generally consistent with the known profile of Sorafenib. The most common treatment-emergent adverse events in the Sorafenib arm were hand-foot skin reaction, diarrhea, alopecia, rash / desquamation, fatigue, weight loss and hypertension.

The DECISION ( stuDy of sorafEnib in loCally advanced or metastatIc patientS with radioactive Iodine refractory thyrOid caNcer ) trial was an international, multicenter, placebo-controlled study. A total of 417 patients with locally advanced or metastatic, RAI-refractory, differentiated thyroid cancer ( papillary, follicular, Hürthle cell and poorly differentiated ) who had received no prior chemotherapy, tyrosine kinase inhibitors, monoclonal antibodies that target VEGF or VEGF receptor, or other targeted agents for thyroid cancer were randomized to receive 400 mg of oral Sorafenib twice daily ( 207 patients ) or matching placebo ( 210 patients ).
Ninety-six percent of randomized patients had metastatic disease.

Thyroid cancer has become the fastest-increasing cancer in the world in recent years and is the sixth most common cancer in women. There are more than 213,000 new cases of thyroid cancer annually, and approximately 35,000 people die worldwide each year.

Papillary, follicular and Hürthle cell types of thyroid cancer are classified as differentiated thyroid cancer and account for approximately 94% of all thyroid cancers. While the majority of differentiated thyroid cancers are treatable, RAI-refractory locally advanced or metastatic disease is more difficult to treat and is associated with a lower patient survival rate.

In preclinical studies, Sorafenib has been shown to inhibit multiple kinases thought to be involved in both cell proliferation and angiogenesis, two important processes that enable cancer growth. These kinases included Raf kinase, VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-B, KIT, FLT-3 and RET.

Source: 49th Annual Meeting of American Society of Clinical Oncology ( ASCO ), 2013

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