Bayer and Onyx Report Phase 3 Study Results of NEXAVAR® (sorafenib) as Adjuvant Treatment for Patients with Liver Cancer Who Have Undergone Surgery or Local Ablation
WHIPPANY, N.J., THOUSAND OAKS, Calif. and SOUTH SAN FRANCISCO, Calif., March 11, 2014 /PRNewswire/ -- Bayer HealthCare Pharmaceuticals Inc. and Onyx Pharmaceuticals, Inc., an Amgen subsidiary (Nasdaq: AMGN), today announced that a Phase 3 trial evaluating the investigational use of NEXAVAR®(sorafenib) tablets as an adjuvant treatment for patients with hepatocellular carcinoma (HCC), or liver cancer, who had no detectable disease after surgical resection or local ablation, did not meet its primary endpoint of improving recurrence-free survival. The safety findings were consistent with the known profile of sorafenib. Data from this study will be submitted for presentation at an upcoming scientific congress.
"While the primary endpoint of this adjuvant trial was not met, Bayer and Onyx remain dedicated to ongoing research in all stages of liver cancer," said Pamela A. Cyrus, M.D., Vice President and Head of U.S. Medical Affairs, Bayer HealthCare Pharmaceuticals. "The outcome announced today does not affect the currently approved indications. NEXAVAR is approved for the treatment of patients with unresectable liver cancer."
Full prescribing information for NEXAVAR is available at www.NEXAVAR-us.com.
About the STORM Trial
The Phase 3, randomized, double-blind, placebo-controlled STORM (Sorafenib as Adjuvant Treatment in the Prevention of Recurrence of Hepatocellular Carcinoma) trial is an international multicenter study that evaluated clinical benefit of sorafenib versus placebo as an adjuvant treatment in patients with HCC following potential curative treatment (surgical resection or local ablation). The primary endpoint of the study was recurrence-free survival (i.e., the length of time that a patient survives without recurrence of HCC). Secondary endpoints included time to recurrence of HCC (intrahepatic and extrahepatic) and overall survival. Safety and tolerability were also assessed. The trial included approximately 1,100 patients who were randomized to receive 400 mg of sorafenib twice daily or matching placebo for four years or until disease recurrence, whichever occurred first.
About Liver Cancer
Hepatocellular carcinoma is the most common form of liver cancer and is responsible for about 80 percent of the primary malignant liver tumors in adults.1,2 Liver cancer is the sixth most common cancer in the world and is the second most common cause of death from cancer worldwide. More than 780,000 cases of liver cancer are diagnosed worldwide each year (more than 395,000 in China, 52,000 in the European Union and 30,000 in the United States) and the incidence is increasing. In 2012, approximately 746,000 people died of liver cancer including approximately 383,000 in China, 48,000 in the European Union and 24,000 in the United States.3
About NEXAVAR® (sorafenib) Tablets
NEXAVAR is approved in the U.S. for the treatment of patients with unresectable hepatocellular carcinoma, patients with advanced renal cell carcinoma and patients with locally recurrent or metastatic, progressive, differentiated thyroid carcinoma refractory to radioactive iodine treatment. NEXAVAR is thought to inhibit both the tumor cell and tumor vasculature. In in vitro studies, NEXAVAR has been shown to inhibit multiple kinases thought to be involved in both cell proliferation (growth) and angiogenesis (blood supply) - two important processes that enable cancer growth. These kinases include Raf kinase, VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-B, KIT, FLT-3 and RET.
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 Japan where Bayer manages all development. The companies co-promote NEXAVAR in the U.S. Outside of the U.S. Bayer has exclusive marketing rights, and Bayer and Onyx share profits globally, excluding Japan.
Important Safety Considerations For NEXAVAR® (sorafenib) Tablets
NEXAVAR in combination with carboplatin and paclitaxel is contraindicated in patients with squamous cell lung cancer.
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 Stevens-Johnson syndrome or toxic epidermal necrolysis are suspected as these may be life-threatening.
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).
About Bayer HealthCare Pharmaceuticals Inc.
Bayer HealthCare Pharmaceuticals Inc. is the U.S.-based pharmaceuticals business of Bayer HealthCare LLC, a subsidiary of Bayer AG. Bayer HealthCare is one of the world's leading, innovative companies in the healthcare and medical products industry, and combines the activities of the Animal Health, Consumer Care, Medical Care, and Pharmaceuticals divisions. As a specialty pharmaceutical company, Bayer HealthCare Pharmaceuticals Inc. provides products for General Medicine, Hematology, Neurology, Oncology and Women's Healthcare. The company's aim is to discover and manufacture products that will improve human health worldwide by diagnosing, preventing and treating diseases.
Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.
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About Onyx Pharmaceuticals, Inc.
Based in South San Francisco, California, Onyx Pharmaceuticals, Inc., an Amgen subsidiary, is a biopharmaceutical company engaged in the development and commercialization of innovative therapies for improving the lives of people with cancer. The company is focused on developing novel medicines that target key molecular pathways. For more information about Onyx, visit the company's website at www.onyx.com. Onyx Pharmaceuticals is on Twitter. Sign up to follow our Twitter feed @OnyxPharm at http://twitter.com/OnyxPharm.
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NEXAVAR® is a registered trademark of Bayer.
1 El-Serag, Hashem, M.D., M.P.H. Current Concepts in Hepatocellular Carcinoma. The New England Journal of Medicine. 2011; 365: 1118-27.
2 Available at American Society of Clinical Oncology: http://www.asco.org/patient/Cancer+Types/Liver+Cancer.
3 Ferlay J, et al., GLOBOCAN 2012. Cancer Incidence, Mortality and Prevalence Worldwide in 2012. Available at:http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx Accessed January 2014.