AMGEN INC. WHIPPANY, N.J., Sept. 24, 2014 /PRNewswire/ -- Bayer HealthCare Pharmaceuticals Inc. announced today that data from its oncology portfolio, including Stivarga(®) (regorafenib) tablets, NEXAVAR(®) (sorafenib) tablets and Xofigo(®) (radium Ra 223 dichloride) injection, will be presented at the European Society for Medical Oncology (ESMO) 2014 Congress taking place September 26 - 30 in Madrid, Spain.
"Bayer's presence at this global medical congress demonstrates our commitment to research in the oncology space, as we continue to explore additional treatment options and further investigate the clinical candidates in our franchise portfolio," said Dario Mirski, M.D., Vice President and Head of U.S. Medical Affairs, Bayer HealthCare Pharmaceuticals.
Notable studies evaluating Bayer's oncology products at ESMO 2014 are listed below.
Regorafenib
-- CONCUR: A randomized, placebo-controlled phase 3 study of regorafenib
(REG) monotherapy in Asian patients with previously treated metastatic
colorectal cancer (mCRC)
-- Oral Presentation 500O, Proffered Paper Session: Gastrointestinal
tumors, colorectal
-- Saturday, September 27, 10:20 - 10:35 AM (CET), Madrid Room
-- REBECCA: A large cohort study of Regorafenib (REG) in the real-life
setting in patients (pts) previously treated for metastatic colorectal
cancer (mCRC)
-- Abstract 602P, Poster Display Session: Gastrointestinal tumors,
colorectal
-- Monday, September 29, 12:45 - 1:45 PM (CET), Poster Area
-- The Cost of Survival Gains in Metastatic Colorectal Cancer (mCRC) in
Four European Countries
-- Abstract 604P_PR, Poster Display Session: Gastrointestinal tumors,
colorectal
-- Monday, September 29, 12:45 - 1:45 PM (CET), Poster Area
-- Adjuvant regorafenib (REG) in stage IV colorectal cancer (CRC) after
curative treatment of liver metastases: a phase III randomized, placebo
(PBO)-controlled trial (COAST)
-- Abstract 611TiP, Poster Display Session: Gastrointestinal tumors,
colorectal
-- Monday, September 29, 12:45 - 1:45 PM (CET), Poster Area
-- A prospective, observational trial to further assess safety and efficacy
of regorafenib in patients with metastatic colorectal cancer (mCRC) in
routine clinical practice (CORRELATE)
-- Abstract 613TiP, Poster Display Session: Gastrointestinal tumors,
colorectal
-- Monday, September 29, 12:45 - 1:45 PM (CET), Poster Area
-- Analysis of treatment patterns of patients with advanced
gastrointestinal stromal tumors (GIST) in EU5
-- Abstract 1427P, Poster Display Session: Sarcoma
-- Monday, September 29, 12:45 - 1:45 PM (CET), Poster Area
Sorafenib
-- Correlation of sorafenib exposure with safety and efficacy from pivotal
clinical trials in hepatocellular carcinoma (HCC) and renal cell cancer
(RCC)
-- Abstract 485P, Poster Display Session: Developmental therapeutics
-- Saturday, September 27, 12:45 - 1:45 PM (CET), Poster Area
-- Health economic analysis of the randomized multicenter phase II trial
SAKK 77/08: sorafenib with or without everolimus in patients with
unresectable hepatocellular carcinoma (HCC)
-- Abstract 1039P, Poster Display Session: Health economics
-- Sunday, September 28, 12:45 - 1:45 PM (CET), Poster Area
-- A phase III randomized, double-blind, trial comparing sorafenib plus
capecitabine versus placebo plus capecitabine in the treatment of
locally advanced or metastatic HER2-negative breast cancer (RESILIENCE)
-- Oral Presentation LBA8, Proffered Paper Session: Breast cancer,
metastatic
-- Sunday, September 28, 2:10 - 3:45 PM (CET), Madrid Room
-- Final analysis of overall survival per subgroups of HCC patients in the
prospective, non-interventional INSIGHT study treated with sorafenib
-- Abstract 728P, Poster Display Session: Gastrointestinal tumors,
non-colorectal
-- Monday, September 29, 12:45 - 1:45 PM (CET), Poster Area
-- An international observational study to assess the use of sorafenib
after transarterial chemoembolization (TACE) in patients with
hepatocellular carcinoma (HCC): OPTIMIS
-- Abstract 743TiP, Poster Display Session: Gastrointestinal tumors,
non-colorectal
-- Monday, September 29, 12:45 - 1:45 PM (CET), Poster Area
Radium Ra 223 Dichloride (radium-223)
-- External-beam radiation therapy (EBRT) use and safety with radium-223
dichloride (Ra) in patients (pts) with castration-resistant prostate
cancer (CRPC) and symptomatic bone metastases (mets) from the ALSYMPCA
trial
-- Abstract 768P, Poster Display Session: Genitourinary tumors,
prostate
-- Saturday, September 27, 12:45 - 1:45 PM, Poster Area
-- 1.5-year post-treatment follow-up of radium-223 dichloride (Ra-223)
safety in patients (pts) with castration-resistant prostate cancer
(CRPC) and symptomatic bone metastases from ALSYMPCA: characterization
of hematologic safety profiles
-- Abstract 769P, Poster Display Session: Genitourinary tumors,
prostate
-- Saturday, September 27, 12:45 - 1:45 PM, Poster Area
-- Reasons for Patients (Pts) Discontinuing Study Treatment (Tx) in the
Phase 3 ALSYMPCA Trial of Radium-223 Dichloride (Ra-223) in
Castration-Resistant Prostate Cancer (CRPC) With Bone Metastases (Mets)
-- Abstract 770P, Poster Display Session: Genitourinary tumors,
prostate
-- Saturday, September 27, 12:45 - 1:45 PM, Poster Area
-- ERA 223--a phase 3 trial of radium-223 dichloride (Ra-223) in
combination with abiraterone acetate (AA) and prednisone in the
treatment of asymptomatic or mildly symptomatic chemotherapy-naive
patients with bone-predominant metastatic castration-resistant prostate
cancer (CRPC)
-- Abstract 803TiP, Poster Display Session: Genitourinary tumors,
prostate
-- Saturday, September 27, 12:45 - 1:45 PM, Poster Area
-- Safety of radium-223 dichloride (Ra) with docetaxel (D) in patients
(pts) with bone metastases (mets) from castration-resistant prostate
cancer (CRPC): a phase 1/2a clinical trial
-- Abstract 765PD, Poster Discussion Session: Genitourinary tumors,
prostate
-- Sunday, September 28, 1:00 - 2:00 PM, Granada Room
About Stivarga(®) (regorafenib) Tablets
In the United States, Stivarga is indicated for the treatment of patients with mCRC who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if KRAS wild type, an anti-EGFR therapy. It is also indicated for the treatment of patients with locally advanced, unresectable or metastatic gastrointestinal stromal tumor (GIST) who have been previously treated with imatinib mesylate and sunitinib malate.(1)
Stivarga is an inhibitor of multiple kinases involved in normal cellular functions and in pathologic processes such as oncogenesis, tumor angiogenesis and maintenance of the tumor microenvironment.(1)
Stivarga is a compound developed by Bayer. In 2011, Bayer entered into an agreement with Onyx Pharmaceuticals, Inc., an Amgen subsidiary (NASDAQ: AMGN), under which Onyx receives a royalty on all global net sales of Stivarga in oncology.
Important Safety Information for Stivarga(®) (regorafenib) Tablets:
WARNING: HEPATOTOXICITY
-- Severe and sometimes fatal hepatotoxicity has been observed in clinical
trials.
-- Monitor hepatic function prior to and during treatment.
-- Interrupt and then reduce or discontinue Stivarga for hepatotoxicity as
manifested by elevated liver function tests or hepatocellular necrosis,
depending upon severity and persistence.
Severe drug-induced liver injury with fatal outcome occurred in 0.3% of 1200 Stivarga-treated patients across all clinical trials. In metastatic colorectal cancer (mCRC), fatal hepatic failure occurred in 1.6% of patients in the Stivarga arm and in 0.4% of patients in the placebo arm; all the patients with hepatic failure had metastatic disease in the liver. In gastrointestinal stromal tumor (GIST), fatal hepatic failure occurred in 0.8% of patients in the Stivarga arm.
Obtain liver function tests (ALT, AST, and bilirubin) before initiation of Stivarga and monitor at least every 2 weeks during the first 2 months of treatment. Thereafter, monitor monthly or more frequently as clinically indicated. Monitor liver function tests weekly in patients experiencing elevated liver function tests until improvement to less than 3 times the upper limit of normal (ULN) or baseline values. Temporarily hold and then reduce or permanently discontinue Stivarga, depending on the severity and persistence of hepatotoxicity as manifested by elevated liver function tests or hepatocellular necrosis.
Stivarga caused an increased incidence of hemorrhage. The overall incidence (Grades 1-5) was 21% and 11% with Stivarga vs 8% and 3% with placebo in mCRC and GIST patients, respectively. Fatal hemorrhage occurred in 4 of 632 (0.6%) Stivarga-treated patients and involved the respiratory, gastrointestinal, or genitourinary tracts. Permanently discontinue Stivarga in patients with severe or life-threatening hemorrhage and monitor INR levels more frequently in patients receiving warfarin.
Stivarga caused an increased incidence of hand-foot skin reaction (HFSR) (also known as palmar-plantar erythrodysesthesia [PPE]) and severe rash, frequently requiring dose modification. The overall incidence was 45% and 67% with Stivarga vs 7% and 12% with placebo in mCRC and GIST patients, respectively. Incidence of Grade 3 HFSR (17% vs 0% in mCRC and 22% vs 0% in GIST), Grade 3 rash (6% vs <1% in mCRC and 7% vs 0% in GIST), serious adverse reactions of erythema multiforme (0.2% vs 0% in mCRC), and Stevens-Johnson syndrome (0.2% vs 0% in mCRC) was higher in Stivarga-treated patients. Toxic epidermal necrolysis occurred in 0.17% of 1200 Stivarga-treated patients across all clinical trials. Withhold Stivarga, reduce the dose, or permanently discontinue depending on the severity and persistence of dermatologic toxicity.
Stivarga caused an increased incidence of hypertension (30% vs 8% in mCRC and 59% vs 27% in GIST with Stivarga vs placebo, respectively). Hypertensive crisis occurred in 0.25% of 1200 Stivarga-treated patients across all clinical trials. Do not initiate Stivarga until blood pressure is adequately controlled. Monitor blood pressure weekly for the first 6 weeks of treatment and then every cycle, or more frequently, as clinically indicated. Temporarily or permanently withhold Stivarga for severe or uncontrolled hypertension.
Stivarga increased the incidence of myocardial ischemia and infarction in mCRC (1.2% with Stivarga vs 0.4% with placebo). Withhold Stivarga in patients who develop new or acute cardiac ischemia or infarction, and resume only after resolution of acute cardiac ischemic events if the potential benefits outweigh the risks of further cardiac ischemia.
Reversible Posterior Leukoencephalopathy Syndrome (RPLS) occurred in 1 of 1200 Stivarga-treated patients across all clinical trials. Perform an evaluation for RPLS in any patient presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Confirm the diagnosis of RPLS with MRI and discontinue Stivarga in patients who develop RPLS.
Gastrointestinal perforation or fistula occurred in 0.6% of 1200 patients treated with Stivarga across clinical trials. In GIST, 2.1% (4/188) of Stivarga-treated patients developed gastrointestinal fistula or perforation: of these, 2 cases of gastrointestinal perforation were fatal. Permanently discontinue Stivarga in patients who develop gastrointestinal perforation or fistula.
Treatment with Stivarga should be stopped at least 2 weeks prior to scheduled surgery. Resuming treatment after surgery should be based on clinical judgment of adequate wound healing. Stivarga should be discontinued in patients with wound dehiscence.
Stivarga can cause fetal harm when administered to a pregnant woman. Use effective contraception during treatment and up to 2 months after completion of therapy. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.
Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Stivarga, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
The most frequently observed adverse drug reactions (greater than or equal to 30%) in Stivarga-treated patients vs placebo-treated patients in mCRC, respectively, were: asthenia/fatigue (64% vs 46%), decreased appetite and food intake (47% vs 28%), HFSR/PPE (45% vs 7%), diarrhea (43% vs 17%), mucositis (33% vs 5%), weight loss (32% vs 10%), infection (31% vs 17%), hypertension (30% vs 8%), and dysphonia (30% vs 6%).
The most frequently observed adverse drug reactions (greater than or equal to 30%) in Stivarga-treated patients vs placebo-treated patients in GIST, respectively, were: HFSR/PPE (67% vs 15%), hypertension (59% vs 27%), asthenia/fatigue (52% vs 39%), diarrhea (47% vs 9%), mucositis (40% vs 8%), dysphonia (39% vs 9%), infection (32% vs 5%), decreased appetite and food intake (31% vs 21%), and rash (30% vs 3%).
For full prescribing information, including the Boxed Warning, visit www.stivarga-us.com.
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.(2 )
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 is contraindicated in patients with known severe
hypersensitivity to sorafenib or any other component of NEXAVAR
-- 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%).There was no Grade 4 bleeding reported and there
was one fatal hemorrhage in a placebo-treated patient. If bleeding
necessitates medical intervention, consider permanent discontinuation of
NEXAVAR. Due to the potential risk of bleeding, tracheal, bronchial, and
esophageal infiltration should be treated with local therapy prior to
administering NEXAVAR in patients with DTC
-- Monitor blood pressure weekly during the first 6 weeks and periodically
thereafter, and treat, if required. In the HCC study, hypertension was
reported in approximately 9.4% of NEXAVAR-treated patients and 4.3% of
patients in the placebo-treated group. In the RCC study, hypertension
was reported in approximately 16.9% of NEXAVAR-treated patients and 1.8%
of patients in the placebo-treated group. In the DTC study, hypertension
was reported in 40.6% of NEXAVAR-treated patients and 12.4% of the
placebo-treated patients. Hypertension was usually mild to moderate,
occurred early in the course of treatment, and was managed with standard
antihypertensive therapy. In cases of severe or persistent hypertension
despite institution of antihypertensive therapy, consider temporary or
permanent discontinuation of NEXAVAR
-- Hand-foot skin reaction and rash are the most common adverse reactions
attributed to NEXAVAR. 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. There have
been reports of severe dermatologic toxicities, including
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).
These cases may be life-threatening. Discontinue NEXAVAR if SJS or TEN
are suspected
-- 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
-- Infrequent bleeding or elevations in the International Normalized Ratio
(INR) have been reported in some patients taking warfarin while on
NEXAVAR. Monitor patients taking concomitant warfarin regularly for
changes in prothrombin time (PT), INR, or clinical bleeding episodes
-- Temporary interruption of NEXAVAR therapy is recommended in patients
undergoing major surgical procedures
-- In a subset analysis of two randomized controlled trials in chemo-naive
patients with Stage IIIB-IV non-small cell lung cancer, patients with
squamous cell carcinoma experienced higher mortality with the addition
of NEXAVAR compared to those treated with carboplatin/paclitaxel alone
(HR 1.81, 95% CI 1.19-2.74) and gemcitabine/cisplatin alone (HR 1.22,
95% CI 0.82-1.80). 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 electrolytes and electrocardiograms in patients
with congestive heart failure, bradyarrhythmias, drugs known to prolong
the QT interval, including Class Ia and III antiarrhythmics, and
electrolyte abnormalities. Correct electrolyte abnormalities (magnesium,
potassium, calcium). Interrupt NEXAVAR if QTc interval is greater than
500 milliseconds or for an increase from baseline of 60 milliseconds or
greater
-- Sorafenib-induced hepatitis is characterized by a hepatocellular pattern
of liver damage with significant increases of transaminases which may
result in hepatic failure and death. Increases in bilirubin and INR may
also occur. 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
-- Female patients should 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. For patients with impaired TSH suppression
while receiving NEXAVAR, the median maximal TSH was 1.6 mU/L and 25% had
TSH levels greater than 4.4 mU/L. Monitor TSH levels monthly and adjust
thyroid replacement medication as needed in patients with DTC
-- In the HCC study, the most common laboratory abnormalities observed in
the NEXAVAR arm versus the placebo arm, respectively, were
hypoalbuminemia (59% vs. 47%), lymphopenia (47% vs. 42%),
thrombocytopenia (46% vs. 41%), elevation in INR (42% vs. 34%), elevated
lipase (40% vs. 37%), hypophosphatemia (35% vs. 11%), elevated amylase
(34% vs. 29%), hypocalcemia (27% vs. 15%), and hypokalemia (9.5% vs.
5.9%)
-- In the RCC study, the most common laboratory abnormalities observed in
the NEXAVAR arm versus the placebo arm, respectively, were
hypophosphatemia (45% vs. 11%), anemia (44% vs. 49%), elevated lipase
(41% vs. 30%), elevated amylase (30% vs. 23%), lymphopenia (23% vs.
13%), neutropenia (18% vs. 10%), thrombocytopenia (12% vs. 5%),
hypocalcemia (12% vs. 8%), and hypokalemia (5.4% vs. 0.7%)
-- In the DTC study, the most common laboratory abnormalities observed in
the NEXAVAR arm versus the placebo arm, respectively, were elevated ALT
(59% vs. 24%), elevated AST (54% vs. 15%), and hypocalcemia (36% vs.
11%).The relative increase for the following laboratory abnormalities
observed in NEXAVAR-treated DTC patients as compared to placebo-treated
patients is similar to that observed in the RCC and HCC studies: lipase,
amylase, hypokalemia, hypophosphatemia, neutropenia, lymphopenia,
anemia, and thrombocytopenia
-- 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 Xofigo(®) (radium Ra 223 dichloride) Injection
Xofigo is indicated for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastatic disease.
Xofigo is an alpha particle-emitting radioactive therapeutic agent with an anti-tumor effect on bone metastases. The active ingredient in Xofigo is the alpha particle-emitting isotope radium-223, which mimics calcium and forms complexes with the bone mineral hydroxyapatite at areas of increased bone turnover, such as bone metastases. The high linear energy transfer of Xofigo may cause double-strand DNA breaks in adjacent cells, resulting in an anti-tumor effect on bone metastases. The alpha particle range from radium Ra 223 dichloride is less than 100 micrometers which may limit the damage to the surrounding normal tissue.(3)
Important Safety Information for Xofigo(®) (radium Ra 223 dichloride) Injection
-- Contraindications: Xofigo is contraindicated in women who are or may
become pregnant. Xofigo can cause fetal harm when administered to a
pregnant woman.
-- Bone Marrow Suppression: In the randomized trial, 2% of patients in the
Xofigo arm experienced bone marrow failure or ongoing pancytopenia,
compared to no patients treated with placebo. There were two deaths due
to bone marrow failure. For 7 of 13 patients treated with Xofigo bone
marrow failure was ongoing at the time of death. Among the 13 patients
who experienced bone marrow failure, 54% required blood transfusions.
Four percent (4%) of patients in the Xofigo arm and 2% in the placebo
arm permanently discontinued therapy due to bone marrow suppression. In
the randomized trial, deaths related to vascular hemorrhage in
association with myelosuppression were observed in 1% of Xofigo-treated
patients compared to 0.3% of patients treated with placebo. The
incidence of infection-related deaths (2%), serious infections (10%),
and febrile neutropenia (<1%) was similar for patients treated with
Xofigo and placebo. Myelosuppression - notably thrombocytopenia,
neutropenia, pancytopenia, and leucopenia - has been reported in
patients treated with Xofigo.Monitor patients with evidence of
compromised bone marrow reserve closely and provide supportive care
measures when clinically indicated. Discontinue Xofigo in patients who
experience life-threatening complications despite supportive care for
bone marrow failure.
-- Hematological Evaluation: Monitor blood counts at baseline and prior to
every dose of Xofigo. Prior to first administering Xofigo, the absolute
neutrophil count (ANC) should be greater than or equal to 1.5 ×
10(9)/L, the platelet count greater than or equal to 100 × 10(9)/L, and
hemoglobin greater than or equal to 10 g/dL. Prior to subsequent
administrations, the ANC should be greater than or equal to 1 × 10(9)/L
and the platelet count greater than or equal to 50 × 10(9)/L.
Discontinue Xofigo if hematologic values do not recover within 6 to 8
weeks after the last administration despite receiving supportive care.
-- Concomitant Use with Chemotherapy: Safety and efficacy of concomitant
chemotherapy with Xofigo have not been established. Outside of a
clinical trial, concomitant use of Xofigo in patients on chemotherapy is
not recommended due to the potential for additive myelosuppression. If
chemotherapy, other systemic radioisotopes, or hemibody external
radiotherapy are administered during the treatment period, Xofigo should
be discontinued.
-- Administration and Radiation Protection: Xofigo should be received,
used, and administered only by authorized persons in designated clinical
settings. The administration of Xofigo is associated with potential
risks to other persons from radiation or contamination from spills of
bodily fluids such as urine, feces, or vomit. Therefore, radiation
protection precautions must be taken in accordance with national and
local regulations.
-- Fluid Status: Dehydration occurred in 3% of patients on Xofigo and 1% of
patients on placebo. Xofigo increases adverse reactions such as
diarrhea, nausea, and vomiting, which may result in dehydration. Monitor
patients' oral intake and fluid status carefully and promptly treat
patients who display signs or symptoms of dehydration or hypovolemia.
-- Injection Site Reactions: Erythema, pain, and edema at the injection
site were reported in 1% of patients on Xofigo.
-- Secondary Malignant Neoplasms: Xofigo contributes to a patient's overall
long-term cumulative radiation exposure. Long-term cumulative radiation
exposure may be associated with an increased risk of cancer and
hereditary defects. Due to its mechanism of action and neoplastic
changes, including osteosarcomas, in rats following administration of
radium -223 dichloride, Xofigo may increase the risk of osteosarcoma or
other secondary malignant neoplasms. However, the overall incidence of
new malignancies in the randomized trial was lower on the Xofigo arm
compared to placebo (<1% vs 2%; respectively), but the expected latency
period for the development of secondary malignancies exceeds the
duration of follow up for patients on the trial.
-- Subsequent Treatment with Cytotoxic Chemotherapy: In the randomized
clinical trial, 16% patients in the Xofigo group and 18% patients in the
placebo group received cytotoxic chemotherapy after completion of study
treatments. Adequate safety monitoring and laboratory testing was not
performed to assess how patients treated with Xofigo will tolerate
subsequent cytotoxic chemotherapy.
-- Adverse Reactions: The most common adverse reactions (greater than or
equal to 10%) in the Xofigo arm vs the placebo arm, respectively, were
nausea (36% vs 35%), diarrhea (25% vs 15%), vomiting (19% vs 14%), and
peripheral edema (13% vs 10%). Grade 3 and 4 adverse events were
reported in 57% of Xofigo-treated patients and 63% of placebo-treated
patients. The most common hematologic laboratory abnormalities in the
Xofigo arm (greater than or equal to 10%) vs the placebo arm,
respectively, were anemia (93% vs 88%), lymphocytopenia (72% vs 53%),
leukopenia (35% vs 10%), thrombocytopenia (31% vs 22%), and neutropenia
(18% vs 5%).
For full prescribing information visit http://labeling.bayerhealthcare.com/html/products/pi/Xofigo_PI.pdf.
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 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.
© 2014 Bayer HealthCare Pharmaceuticals Inc.
BAYER, the Bayer Cross, NEXAVAR, Stivarga and Xofigo are registered trademarks of Bayer.
Forward-Looking Statement
This news 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 www.bayer.com. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.
1. STIVARGA(R) (regorafenib) [Prescribing Information]. Wayne, NJ: Bayer HealthCare Pharmaceuticals, August 2013.
2. NEXAVAR(R) (sorafenib) [Prescribing Information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, November 2013.
3. XOFIGO(R) (radium Ra 223 dichloride) [Prescribing Information]. Wayne, NJ: Bayer HealthCare Pharmaceuticals, May 2013.
PP-750-US-0005
Intended for U.S. Media Only
SOURCE Bayer HealthCare Pharmaceuticals Inc.
