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
BERLIN, Germany I April 24, 2014 I 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.
About Thyroid Cancer
Thyroid cancer is the most common endocrine malignancy.(1) There are more than 298,000 new cases of thyroid cancer annually and nearly 40,000 people die from thyroid cancer worldwide each year.(2)
Papillary, follicular (including Hürthle cell) and poorly differentiated types of thyroid cancer are classified as “differentiated thyroid cancer” and account for approximately 94 percent of all thyroid cancers.(3) 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.(3,4)
About Nexavar® (sorafenib)
Nexavar® (sorafenib), an oral anti-cancer therapy, is currently approved in more than 100 countries worldwide. In Europe, it is approved for the treatment of hepatocellular carcinoma (HCC) and for the treatment of patients with advanced renal cell carcinoma (RCC) who have failed prior interferon-alpha or interleukin-2 based therapy or are considered unsuitable for such therapy. Nexavar is also approved in the United States for the treatment of patients with locally recurrent or metastatic, progressive, differentiated thyroid cancer (DTC) that is refractory to radioactive iodine treatment.
In preclinical 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 also being evaluated by Bayer and Onyx, international study groups, government agencies and individual investigators in a range of other cancers.
Nexavar is co-developed by Onyx Pharmaceuticals, Inc., an Amgen subsidiary, 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.
About Oncology at Bayer
Bayer is committed to delivering science for a better life by advancing a portfolio of innovative treatments. The oncology franchise at Bayer now includes three oncology products and several other compounds in various stages of clinical development. Together, these products reflect the company’s approach to research, which prioritizes targets and pathways with the potential to impact the way that cancer is treated.
About Bayer HealthCare
The Bayer Group is a global enterprise with core competencies in the fields of health care, agriculture and high-tech materials. Bayer HealthCare, a subgroup of Bayer AG with annual sales of EUR 18.9 billion (2013), is one of the world’s leading, innovative companies in the healthcare and medical products industry and is based in Leverkusen, Germany. The company combines the global activities of the Animal Health, Consumer Care, Medical Care and Pharmaceuticals divisions. Bayer HealthCare’s aim is to discover, develop, manufacture and market products that will improve human and animal health worldwide. Bayer HealthCare has a global workforce of 56,000 employees (Dec 31, 2013) and is represented in more than 100 countries. More information is available at http://www.healthcare.bayer.com.
Our online press service is just a click away: http://press.healthcare.bayer.com
Follow us on Facebook: http://www.facebook.com/healthcare.bayer
Follow us on Twitter: https://twitter.com/BayerHealthCare
Find more information at http://www.bayerpharma.com.
Forward-Looking Statements
This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer Group or subgroup management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer’s public reports which are available on the Bayer website at http://www.bayer.com. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.
References:
(1) National Cancer Institute. “General Information about Thyroid Cancer.” http://www.cancer.gov/cancertopics/pdq/treatment/thyroid/healthprofessional. Accessed January 10, 2014.
(2) World Health Organization: GLOBOCAN 2012. Cancer Incidence and Mortality Worldwide in 2012. http://globocan.iarc.fr/Pages/fact_sheets_population.aspx. Accessed February 24, 2014.
(3) Naifa Lamki Busaidy and Maria E. Cabanillas, “Differentiated Thyroid Cancer: Management of Patients with Radioiodine Nonresponsive Disease,” Journal of Thyroid Research, vol. 2012.
(4) Lucia Brilli, Furio Pacini. Future Oncology. Targeted Therapy in Refractory Thyroid Cancer. 2011;7(5):657-668.
SOURCE: Bayer HealthCare
Post Views: 40
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
BERLIN, Germany I April 24, 2014 I 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.
About Thyroid Cancer
Thyroid cancer is the most common endocrine malignancy.(1) There are more than 298,000 new cases of thyroid cancer annually and nearly 40,000 people die from thyroid cancer worldwide each year.(2)
Papillary, follicular (including Hürthle cell) and poorly differentiated types of thyroid cancer are classified as “differentiated thyroid cancer” and account for approximately 94 percent of all thyroid cancers.(3) 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.(3,4)
About Nexavar® (sorafenib)
Nexavar® (sorafenib), an oral anti-cancer therapy, is currently approved in more than 100 countries worldwide. In Europe, it is approved for the treatment of hepatocellular carcinoma (HCC) and for the treatment of patients with advanced renal cell carcinoma (RCC) who have failed prior interferon-alpha or interleukin-2 based therapy or are considered unsuitable for such therapy. Nexavar is also approved in the United States for the treatment of patients with locally recurrent or metastatic, progressive, differentiated thyroid cancer (DTC) that is refractory to radioactive iodine treatment.
In preclinical 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 also being evaluated by Bayer and Onyx, international study groups, government agencies and individual investigators in a range of other cancers.
Nexavar is co-developed by Onyx Pharmaceuticals, Inc., an Amgen subsidiary, 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.
About Oncology at Bayer
Bayer is committed to delivering science for a better life by advancing a portfolio of innovative treatments. The oncology franchise at Bayer now includes three oncology products and several other compounds in various stages of clinical development. Together, these products reflect the company’s approach to research, which prioritizes targets and pathways with the potential to impact the way that cancer is treated.
About Bayer HealthCare
The Bayer Group is a global enterprise with core competencies in the fields of health care, agriculture and high-tech materials. Bayer HealthCare, a subgroup of Bayer AG with annual sales of EUR 18.9 billion (2013), is one of the world’s leading, innovative companies in the healthcare and medical products industry and is based in Leverkusen, Germany. The company combines the global activities of the Animal Health, Consumer Care, Medical Care and Pharmaceuticals divisions. Bayer HealthCare’s aim is to discover, develop, manufacture and market products that will improve human and animal health worldwide. Bayer HealthCare has a global workforce of 56,000 employees (Dec 31, 2013) and is represented in more than 100 countries. More information is available at http://www.healthcare.bayer.com.
Our online press service is just a click away: http://press.healthcare.bayer.com
Follow us on Facebook: http://www.facebook.com/healthcare.bayer
Follow us on Twitter: https://twitter.com/BayerHealthCare
Find more information at http://www.bayerpharma.com.
Forward-Looking Statements
This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer Group or subgroup management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer’s public reports which are available on the Bayer website at http://www.bayer.com. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.
References:
(1) National Cancer Institute. “General Information about Thyroid Cancer.” http://www.cancer.gov/cancertopics/pdq/treatment/thyroid/healthprofessional. Accessed January 10, 2014.
(2) World Health Organization: GLOBOCAN 2012. Cancer Incidence and Mortality Worldwide in 2012. http://globocan.iarc.fr/Pages/fact_sheets_population.aspx. Accessed February 24, 2014.
(3) Naifa Lamki Busaidy and Maria E. Cabanillas, “Differentiated Thyroid Cancer: Management of Patients with Radioiodine Nonresponsive Disease,” Journal of Thyroid Research, vol. 2012.
(4) Lucia Brilli, Furio Pacini. Future Oncology. Targeted Therapy in Refractory Thyroid Cancer. 2011;7(5):657-668.
SOURCE: Bayer HealthCare
Post Views: 40
