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|U.S. FDA Approves NEXAVAR® (sorafenib) for the Treatment of Patients with Locally Recurrent or Metastatic, Progressive, Differentiated Thyroid Carcinoma Refractory to Radioactive Iodine Treatment|
"Locally recurrent or metastatic, progressive, differentiated thyroid carcinoma that is refractory to radioactive iodine treatment is difficult to treat," said
"We are pleased to be able to offer NEXAVAR as a treatment option for patients with thyroid cancer who are no longer responding to standard therapy," said
"An unmet medical need exists for this type of thyroid cancer, underscoring the need for new therapies," said
"The DECISION trial results show sorafenib's ability to extend progression-free survival compared to placebo in patients with this type of advanced thyroid cancer," said
A total of 417 patients with locally recurrent or metastatic, progressive differentiated thyroid carcinoma refractory to radioactive iodine treatment were randomized to receive 400 mg of oral sorafenib twice daily (207 patients) or matching placebo (210 patients). Metastases were present in 96% of the patients: lungs in 86%, lymph nodes in 51%, and bone in 27%.
Sorafenib significantly extended progression-free survival (PFS), the primary endpoint of the study. The median PFS was 10.8 months (95% CI 9.1-12.9) among patients treated with sorafenib compared to 5.8 months (95% CI 5.3-7.8) among patients receiving placebo (HR=0.59 [95% CI, 0.46, 0.76]; p<0.001). PFS was evaluated by an independent radiological review committee using modified Response Evaluation Criteria in Solid Tumors (mRECIST).
Safety and tolerability were also evaluated. The most common adverse reactions reported for NEXAVAR-treated patients vs. placebo-treated patients in DTC, respectively, were: Palmar-plantar erythrodysesthesia syndrome (PPES) (69% vs. 8%), diarrhea (68% vs. 15%), alopecia (67% vs. 8%), weight loss (49% vs. 14%), fatigue (41% vs. 20%), hypertension (41% vs. 12%), rash (35% vs. 7%), decreased appetite (30% vs. 5%), stomatitis (24% vs. 3%), nausea (21% vs. 12%), pruritus (20% vs. 11%), and abdominal pain (20% vs. 7%). Grade 3/4 adverse reactions were 65% vs. 30%. Drug-related adverse reactions that resulted in treatment discontinuation were reported in 14% of NEXAVAR-treated patients compared to 1.4% of placebo-treated patients.
About Thyroid Cancer
Papillary, follicular and Hurthle cell types of thyroid cancer are classified as "differentiated thyroid cancer" and account for approximately 94 percent of all thyroid cancers.4 While the majority of differentiated thyroid cancers are treatable, locally recurrent or metastatic, progressive, differentiated thyroid carcinoma refractory to radioactive iodine treatment is more difficult to treat.4,5
About NEXAVAR® (sorafenib) Tablets
NEXAVAR is currently approved in more than 100 countries. NEXAVAR is also being evaluated by Bayer and Onyx, international study groups, government agencies and individual investigators in a range of cancers.
NEXAVAR is co-developed by Onyx and Bayer, except in
Onyx and Bayer offer a patient assistance program REACH (Resources for Expert Assistance and Care Helpline) for patients who are not able to pay for NEXAVAR. The companies also provide financial support to co-pay foundations. For more information, visit www.NEXAVAR-us.com.
Important Safety Considerations For NEXAVAR® (sorafenib) Tablets
Cardiac ischemia and/or myocardial infarction may occur. The incidence of cardiac ischemia/infarction in NEXAVAR-treated vs. placebo-treated patients was 2.7% vs. 1.3%, 2.9% vs. 0.4%, and 1.9% vs. 0% in the HCC, RCC, and DTC studies, respectively. Temporary or permanent discontinuation of NEXAVAR should be considered in patients who develop cardiac ischemia and/or myocardial infarction.
An increased risk of bleeding may occur following NEXAVAR administration. The following bleeding adverse reactions were reported in the NEXAVAR-treated vs. placebo-treated patients, respectively, in the HCC study: bleeding from esophageal varices (2.4% vs. 4%) and bleeding with fatal outcome at any site (2.4% vs. 4%); in the RCC study: bleeding regardless of causality (15.3% vs. 8.2%), Grade 3 bleeding (2.0% vs. 1.3%), Grade 4 bleeding (0% vs. 0.2%), and one fatal hemorrhage in each treatment group; in the DTC study: bleeding (17.4% vs. 9.6%) and Grade 3 bleeding (1% vs. 1.4%). If bleeding necessitates medical intervention, consider permanent discontinuation of NEXAVAR.
Hypertension may occur early in the course of treatment. Monitor blood pressure weekly during the first 6 weeks and periodically thereafter, and treat, if required.
Hand-foot skin reaction and rash are common and management may include topical therapies for symptomatic relief. In cases of any severe or persistent adverse reactions, temporary treatment interruption, dose modification, or permanent discontinuation of NEXAVAR should be considered. NEXAVAR should be discontinued if
Gastrointestinal perforation was an uncommon adverse reaction and has been reported in less than 1% of patients taking NEXAVAR. Discontinue NEXAVAR in the event of a gastrointestinal perforation.
Patients taking concomitant warfarin should be monitored regularly for changes in prothrombin time (PT), International Normalized Ratio (INR), or clinical bleeding episodes.
Temporary interruption of NEXAVAR therapy is recommended in patients undergoing major surgical procedures.
NEXAVAR, in combination with gemcitabine/cisplatin, is not recommended in patients with squamous cell lung cancer. The safety and effectiveness of NEXAVAR has not been established in patients with non-small cell lung cancer.
NEXAVAR can prolong the QT/QTc interval and increase the risk for ventricular arrhythmias. Avoid use in patients with congenital long QT syndrome and monitor patients with congestive heart failure, bradyarrhythmias, drugs known to prolong the QT interval, and electrolyte abnormalities. Interrupt NEXAVAR if QTc interval is greater than 500 milliseconds or for an increase from baseline of 60 milliseconds or greater.
Drug-induced hepatitis with NEXAVAR may result in hepatic failure and death. Liver function tests should be monitored regularly and in cases of increased transaminases without alternative explanation NEXAVAR should be discontinued.
NEXAVAR may cause fetal harm when administered to a pregnant woman. Women of child-bearing potential should be advised to avoid becoming pregnant while on NEXAVAR and female patients should also be advised against breastfeeding while receiving NEXAVAR.
In DTC, NEXAVAR impairs exogenous thyroid suppression. Elevation of thyroid stimulating hormone (TSH) level above 0.5 mU/L was observed in 41% of NEXAVAR-treated patients as compared with 16% of placebo-treated patients in the DTC study. Monitor TSH levels monthly and adjust thyroid replacement medication as needed in patients with DTC.
Elevations in serum lipase and reductions in serum phosphate of unknown etiology have been associated with NEXAVAR.
Avoid concomitant use of strong CYP3A4 inducers, when possible, because inducers can decrease the systemic exposure of sorafenib. NEXAVAR exposure decreases when co-administered with oral neomycin. Effects of other antibiotics on NEXAVAR pharmacokinetics have not been studied.
Most common adverse reactions reported for NEXAVAR-treated patients vs. placebo-treated patients in unresectable HCC, respectively, were: diarrhea (55% vs. 25%), fatigue (46% vs. 45%), abdominal pain (31% vs. 26%), weight loss (30% vs. 10%), anorexia (29% vs. 18%), nausea (24% vs. 20%), and hand-foot skin reaction (21% vs. 3%). Grade 3/4 adverse reactions were 45% vs. 32%.
Most common adverse reactions reported for NEXAVAR-treated patients vs. placebo-treated patients in advanced RCC, respectively, were: diarrhea (43% vs. 13%), rash/desquamation (40% vs. 16%), fatigue (37% vs. 28%), hand-foot skin reaction (30% vs. 7%), alopecia (27% vs. 3%), and nausea (23% vs. 19%). Grade 3/4 adverse reactions were 38% vs. 28%.
Most common adverse reactions reported for NEXAVAR-treated patients vs. placebo-treated patients in DTC, respectively, were: Palmar-plantar erythrodysesthesia syndrome (PPES) (69% vs. 8%), diarrhea (68% vs. 15%), alopecia (67% vs. 8%), weight loss (49% vs. 14%), fatigue (41% vs. 20%), hypertension (41% vs. 12%), rash (35% vs. 7%), decreased appetite (30% vs. 5%), stomatitis (24% vs. 3%), nausea (21% vs. 12%), pruritus (20% vs. 11%), and abdominal pain (20% vs. 7%). Grade 3/4 adverse reactions were 65% vs. 30%.
For information about NEXAVAR including U.S. NEXAVAR prescribing information, visit www.NEXAVAR-us.com or call 1.866.NEXAVAR (1.866.639.2827).
Forward Looking Statements
Amgen Forward Looking Statements
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NEXAVAR® is a registered trademark of
*Editor's note: Dr. Brose has received consulting fees and honoraria from
Media, Rose Talarico, Bayer HealthCare Pharmaceuticals, (862) 404-5302, or Danielle Bertrand, Onyx Pharmaceuticals, Inc., (650) 266-2114, or Investors, Arvind Sood, Amgen, 1-805-447-1060