Positiva resultat för Sorafenib i Fas III studien DECISION på Tyroideacancer

Positive Results from Phase III DECISION Study of Sorafenib in RAI-Refractory Differentiated Thyroid Cancer Published in The Lancet
Sorafenib significantly extended progression-free survival compared to placebo in patients with differentiated thyroid carcinoma (DTC) that is refractory to radioactive iodine treatment (RAI-refractory) / Based on study results, Nexavar is approved in U.S. for RAI-refractory DTC; filing has also been submitted in EU

Bayer HealthCare Pharmaceuticals Inc. and Onyx Pharmaceuticals, Inc., an Amgen subsidiary, announced today that positive data from the pivotal Phase III DECISION trial of sorafenib (Nexavar®) were published online on April 23rd in The Lancet. These data supported U.S. Food and Drug Administration approval of Nexavar for the treatment of patients with locally recurrent or metastatic, progressive, differentiated thyroid carcinoma (DTC) that is refractory to radioactive iodine (RAI) treatment in November 2013. Sorafenib has also been submitted for regulatory review to the European Medicines Agency (EMA) for this indication. In November 2013, sorafenib was granted an orphan drug designation for the treatment of follicular and papillary thyroid cancer by the European Commission.

”As the first Phase III study in RAI-refractory differentiated thyroid cancer to be reported, these positive results represent an advance for patients with this disease who do not currently have a standard therapeutic option,” said Martin Schlumberger, M.D., of Institut Gustave-Roussy in Villejuif, France and co-lead investigator of the DECISION trial. ”The Lancet publication reinforces the efficacy and safety of sorafenib exhibited in the DECISION trial, which led to its approval in the U.S. and supports its EU filing as a potential new treatment option for patients in Europe.”

In DECISION, sorafenib met the primary endpoint of the study by significantly extending progression-free survival (PFS) compared to placebo (HR 0.59; 95% CI, 0.45-0.76; p<0.0001), representing a 41 percent reduction in the risk of progression or death for patients who received sorafenib compared to placebo-treated patients. The median PFS was 10.8 months in patients treated with sorafenib, compared to 5.8 months in patients receiving placebo. Exploratory subgroup analysis of PFS showed consistent improvement in all pre-specified subgroups, including age, sex, geographical region, histology, sites of metastases and tumor burden. There was no statistically significant difference in overall survival (HR 0.80; 95% CI, 0.54-1.19; p=0.14) and median overall survival had not yet been reached at time of analysis, which was expected due to the post-progression crossover from placebo to open-label sorafenib by the majority (71%) of placebo patients upon progression.

A significant improvement of disease control rate (54.1% versus 33.8%, p<0.0001) and of time to progression (HR 0.56; 95% CI, 0.43-0.72; p<0.0001, median: 11.1 months versus 5.7 months) in sorafenib patients versus placebo patients were observed. Additionally, shrinkage of target lesions was seen in a majority of sorafenib-treated patients.

Adverse events were consistent with the known sorafenib safety profile. The most common AEs in the sorafenib arm were hand-foot skin reaction, diarrhea, alopecia, rash/desquamation, fatigue, weight loss and hypertension.

About the DECISION Trial
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 conducted in 77 centers in 18 countries. A total of 417 patients with locally advanced or metastatic, progressive, 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).

The primary endpoint was PFS, assessed every eight weeks using Response Evaluation Criteria in Solid Tumors (RECIST). Secondary endpoints included overall survival, time to progression, objective response rate, disease control rate and duration of response.