SUMMIT, N.J. - Monday, June 2nd 2014
2014 ASCO Annual Meeting
Celgene Corporation (NASDAQ: CELG) today announced updated Overall Survival (OS) results from a post-hoc analysis of its phase III MPACT (Metastatic Pancreatic Adenocarcinoma Clinical Trial) study of ABRAXANE® (paclitaxel protein-bound particles for injectable suspension) (albumin-bound) in combination with gemcitabine in treatment-naïve patients with metastatic pancreatic cancer. A poster discussion of the analysis is scheduled for Sunday, June 1st at 11:30 am CT at the 50th American Society of Clinical Oncology (ASCO) annual meeting in Chicago, Ill.
The extended data cutoff occurred at final database lock in May 2013 and allowed for an OS analysis of mature data from 90% of the patients in the study. The extended analysis showed that ABRAXANE plus gemcitabine demonstrated an improvement in OS in the intent-to-treat population compared to patients that received gemcitabine alone [(median OS of 8.7 vs. 6.6. months) (HR0.72, P<0.0001), a difference of 2.1 months]. The analysis showed survival up to 3.5 years in the ABRAXANE plus gemcitabine group (3% of patients alive vs 0% with gemcitabine alone). One- and 2- year survival rates were consistent with the primary analysis.
The analysis also showed that the treatment effect on OS for pre-specified subgroups analyzed in the trial remained consistent across patient subgroups. Specifically, patients with Karnofsky Performance Status (KPS) KPS 90-100 had a higher median OS on ABRAXANE plus gemcitabine as compared to gemcitabine alone [median OS 9.7 months vs. 7.9 months (HR 0.77, P=0.0053)]. Patients with KPS 70-80 also maintained a benefit [median OS 7.6 months vs. 4.3 months (HR 0.59, P<0.0001)].
This updated analysis also evaluated the prognostic effects of CA19-9 and neutrophil-to-lymphocyte ratio (NLR). Both elevated CA19-9 and elevated NLR were associated with poorer survival. Further, treatment with ABRAXANE plus gemcitabine appeared to reduce the effect of CA19-9 as a poor prognostic factor, as similar overall survival was observed regardless of CA19-9 level.
In the MPACT study, the most common grade = 3 treatment-related adverse events in the study for ABRAXANE plus gemcitabine vs. gemcitabine alone were neutropenia, peripheral neuropathy and fatigue. In the ABRAXANE plus gemcitabine arm 17% of patients had grade 3 peripheral neuropathy (no cases of grade 4; 54% had any-grade peripheral neuropathy). Seven percent of patients on the ABRAXANE plus gemcitabine arm that received the average treatment duration experienced Grade 3 neuropathy. The median time to improvement of grade 3 peripheral neuropathy to grade = 1 was 29 days, and 44% of patients resumed treatment with ABRAXANE. Grade = 3 fatigue occurred in 18% of patients. The primary results of the MPACT study from the pre-specified analysis from September 2012 were published in the New England Journal of Medicine in the October 31st 2013 edition.
Details of the poster presentation at ASCO:
Abstract: #4027/Poster #46: Analyses of updated overall survival (OS) and prognostic effect of neutrophil-to-lymphocyte ratio (NLR) and CA 19-9 from the phase III MPACT study of nab-paclitaxel (nab-P) plus gemcitabine (Gem) versus Gem for patients (pts) with metastatic pancreatic cancer (PC). Poster: Sunday, June 1st, 8:00–11:00AM CDT, Location: E 354b; Poster discussion: Sunday, June 1st, 11:30AM–12:45PM CDT, Location: E Hall D2.
These results are from a post-hoc investigational analysis.
About the MPACT Study
In the MPACT (Metastatic Pancreatic Adenocarcinoma Clinical Trial) study, a Celgene-sponsored, open-label, randomized, international study, a total of 861 patients were randomized 1:1 (431 patients to the ABRAXANE/gemcitabine group and 430 patients to the gemcitabine group). The primary endpoint for the study was overall survival. Secondary endpoints were progression-free survival and overall response rate determined by independent radiological review. Other endpoints included progression-free survival and overall response rate as determined by the investigator, and the safety and tolerability of the combination in this patient population.
About Pancreatic Cancer
Pancreatic cancer is the fourth-leading cause of cancer-related death in the U.S. and Europe. The pancreas is composed of two main cell types: exocrine and endocrine. Adenocarcinoma is a sub-type of exocrine tumors and accounts for about 95% of cancers of the pancreas. For all stages of pancreatic cancer combined, the five-year survival rate in U.S. is about 6% and 5.7% in the EU. For metastatic pancreatic cancer, the five-year survival is approximately 1% in the U.S.
About ABRAXANE®
ABRAXANE is an albumin-bound form of paclitaxel that is manufactured using patented nab® technology. ABRAXANE is formulated with albumin, a human protein, and is free of solvents.
In September 2013, the U.S. FDA approved ABRAXANE as first-line treatment of patients with metastatic adenocarcinoma of the pancreas, in combination with gemcitabine. In December 2013, ABRAXANE in combination with gemcitabine was approved for first-line treatment of adult patients with metastatic adenocarcinoma of the pancreas in Europe.
Important Safety Information Based on Approved U.S. Label
WARNING - NEUTROPENIA
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Do not administer ABRAXANE therapy to patients who have baseline neutrophil counts of less than 1500 cells/mm3. In order to monitor the occurrence of bone marrow suppression, primarily neutropenia, which may be severe and result in infection, it is recommended that frequent peripheral blood cell counts be performed on all patients receiving ABRAXANE
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Note: An albumin form of paclitaxel may substantially affect a drug’s functional properties relative to those of drug in solution. DO NOT SUBSTITUTE FOR OR WITH OTHER PACLITAXEL FORMULATIONS
CONTRAINDICATIONS
Neutrophil Counts
ABRAXANE should not be used in patients who have baseline neutrophil counts of < 1500 cells/mm3
Hypersensitivity
Patients who experience a severe hypersensitivity reaction to ABRAXANE should not be rechallenged with the drug
WARNINGS AND PRECAUTIONS
Hematologic Effects
Bone marrow suppression (primarily neutropenia) is dose-dependent and a dose-limiting toxicity of ABRAXANE. In a clinical study, Grade 3-4 neutropenia occurred in 38% of patients with pancreatic cancer
Monitor for myelotoxicity by performing complete blood cell counts frequently, including prior to dosing on Days 1, 8, and 15 for pancreatic cancer
Do not administer ABRAXANE to patients with baseline absolute neutrophil counts (ANC) of less than 1500 cells/mm3
In patients with adenocarcinoma of the pancreas, withhold ABRAXANE and gemcitabine if the ANC is less than 500 cells/mm3 or platelets are less than 50,000 cells/mm3 and delay initiation of the next cycle if the ANC is less than 1500 cells/mm3 or platelet count is less than 100,000 cells/mm3 on Day 1 of the cycle. Resume treatment with appropriate dose reduction if recommended
Nervous System
Sensory neuropathy is dose- and schedule-dependent
The occurrence of Grade 1 or 2 sensory neuropathy does not generally require dose modification
If = Grade 3 sensory neuropathy develops, withhold ABRAXANE treatment until resolution to = Grade 1 followed by a dose reduction for all subsequent courses of ABRAXANE
Sepsis
Sepsis occurred in 5% of patients with or without neutropenia who received ABRAXANE in combination with gemcitabine
Biliary obstruction or presence of biliary stent were risk factors for severe or fatal sepsis
If a patient becomes febrile (regardless of ANC), initiate treatment with broad-spectrum antibiotics
For febrile neutropenia, interrupt ABRAXANE and gemcitabine until fever resolves and ANC =1500 cells/mm3, then resume treatment at reduced dose levels
Pneumonitis
Pneumonitis, including some cases that were fatal, occurred in 4% of patients receiving ABRAXANE in combination with gemcitabine
Monitor patients for signs and symptoms and interrupt ABRAXANE and gemcitabine during evaluation of suspected pneumonitis
Permanently discontinue treatment with ABRAXANE and gemcitabine upon making a diagnosis of pneumonitis
Hypersensitivity
Severe and sometimes fatal hypersensitivity reactions, including anaphylactic reactions, have been reported
Patients who experience a severe hypersensitivity reaction to ABRAXANE should not be rechallenged with this drug
Hepatic Impairment
Because the exposure and toxicity of paclitaxel can be increased with hepatic impairment, administration of ABRAXANE in patients with hepatic impairment should be performed with caution
For pancreatic adenocarcinoma, ABRAXANE is not recommended for patients with moderate or severe hepatic impairment
Albumin (Human)
ABRAXANE contains albumin (human), a derivative of human blood
Use in Pregnancy: Pregnancy Category D
ABRAXANE can cause fetal harm when administered to a pregnant woman
If this drug is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus
Women of childbearing potential should be advised to avoid becoming pregnant while receiving ABRAXANE
Use in Men
Men should be advised not to father a child while receiving ABRAXANE
ADVERSE REACTIONS
Among the most common (=20%) adverse reactions in the phase III study, those with a =5% higher incidence in the ABRAXANE/gemcitabine group compared with the gemcitabine group are neutropenia (73%, 58%), fatigue (59%, 46%), peripheral neuropathy (54%, 13%), nausea (54%, 48%), alopecia (50%, 5%), peripheral edema (46%, 30%), diarrhea (44%, 24%), pyrexia (41%, 28%), vomiting (36%, 28%), decreased appetite (36%, 26%), rash (30%, 11%), and dehydration (21%, 11%)
Of these most common adverse reactions, those with a =2% higher incidence of Grade 3-4 toxicity in the ABRAXANE/gemcitabine group compared with the gemcitabine group, respectively, are neutropenia (38%, 27%), fatigue (18%, 9%), peripheral neuropathy (17%, 1%), nausea (6%, 3%), diarrhea (6%, 1%), pyrexia (3%, 1%), vomiting (6%, 4%), decreased appetite (5%, 2%), and dehydration (7%, 2%)
Thrombocytopenia (all grades) was reported in 74% of patients in the ABRAXANE/gemcitabine group vs 70% of patients in the gemcitabine group
The most common serious adverse reactions of ABRAXANE (with a =1% higher incidence) are pyrexia (6%), dehydration (5%), pneumonia (4%), and vomiting (4%)
The most common adverse reactions resulting in permanent discontinuation of ABRAXANE were peripheral neuropathy (8%), fatigue (4%), and thrombocytopenia (2%)
The most common adverse reactions resulting in dose reduction of ABRAXANE are neutropenia (10%) and peripheral neuropathy (6%)
The most common adverse reactions leading to withholding or delay in ABRAXANE dosing are neutropenia (16%), thrombocytopenia (12%), fatigue (8%), peripheral neuropathy (15%), anemia (5%), and diarrhea (5%)
Other selected adverse reactions with a =5% higher incidence for all-grade toxicity in the ABRAXANE/gemcitabine group compared to the gemcitabine group, respectively, are asthenia (19%, 13%), mucositis (10%, 4%), dysgeusia (16%, 8%), headache (14%, 9%), hypokalemia (12%, 7%), cough (17%, 7%), epistaxis (15%, 3%), urinary tract infection (11%, 5%), pain in extremity (11%, 6%), arthralgia (11%, 3%), myalgia (10%, 4%), and depression (12%, 6%)
Other selected adverse reactions with a =2% higher incidence for Grade 3-4 toxicity in the ABRAXANE/gemcitabine group compared to the gemcitabine group are thrombocytopenia (13%, 9%), asthenia (7%, 4%), and hypokalemia (4%, 1%)
Postmarketing Experience With ABRAXANE and Other Paclitaxel Formulations
Severe and sometimes fatal hypersensitivity reactions have been reported with ABRAXANE. The use of ABRAXANE in patients previously exhibiting hypersensitivity to paclitaxel injection or human albumin has not been studied
There have been reports of congestive heart failure, left ventricular dysfunction, and atrioventricular block with ABRAXANE, primarily among individuals with underlying cardiac history or prior exposure to cardiotoxic drugs
There have been reports of extravasation of ABRAXANE. Given the possibility of extravasation, it is advisable to monitor closely the ABRAXANE infusion site for possible infiltration during drug administration
DRUG INTERACTIONS
Caution should be exercised when administering ABRAXANE concomitantly with medicines known to inhibit or induce either CYP2C8 or CYP3A4
USE IN SPECIFIC POPULATIONS
Nursing Mothers
It is not known whether paclitaxel is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother
Pediatric
The safety and effectiveness of ABRAXANE in pediatric patients have not been evaluated
Geriatric
Diarrhea, decreased appetite, dehydration, and epistaxis were more frequent in patients 65 years or older compared with patients younger than 65 years old who received ABRAXANE and gemcitabine in adenocarcinoma of the pancreas
Renal Impairment
The use of ABRAXANE has not been studied in patients with renal impairment
DOSAGE AND ADMINISTRATION
Withhold ABRAXANE if bilirubin =1.26 x ULN or if AST > 10 x ULN
Dose reductions or discontinuation may be needed based on severe hematologic, neurologic, cutaneous, or gastrointestinal toxicity
Monitor patients closely
Please see full Prescribing Information, including Boxed WARNING at http://abraxane.com/downloads/Abraxane_PrescribingInformation.pdf
About Celgene
Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global pharmaceutical company engaged primarily in the discovery, development and commercialization of innovative therapies for the treatment of cancer and inflammatory diseases through gene and protein regulation. For more information, please visit www.celgene.com. Follow us on Twitter @Celgene as well.
Forward-Looking Statements
This press release contains forward-looking statements, which are generally statements that are not historical facts. Forward-looking statements can be identified by the words "expects," "anticipates," "believes," "intends," "estimates," "plans," "will," “outlook” and similar expressions. Forward-looking statements are based on management’s current plans, estimates, assumptions and projections, and speak only as of the date they are made. Celgene Corporation undertakes no obligation to update any forward-looking statement in light of new information or future events, except as otherwise required by law. Forward-looking statements involve inherent risks and uncertainties, most of which are difficult to predict and are generally beyond our control. Actual results or outcomes may differ materially from those implied by the forward-looking statements as a result of the impact of a number of factors, many of which are discussed in more detail in Celgene Corporation’s Annual Report on Form 10-K and its other reports filed with the Securities and Exchange Commission.
Contacts
For Celgene:
Investors:
908-673-9628
investors@celgene.com
Media:
908-673-2275
media@celgene.com
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