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Posted on Dec 11, 04:57PM | IBNS
Celgene Corporation (NASDAQ: CELG), an integrated global biopharmaceutical company, announced the U.S. Food and Drug Administration (FDA) has approved ABRAXANE (paclitaxel protein-bound particles for injectable suspension) (albumin-bound) for the first-line treatment of locally advanced or metastatic non-small cell lung cancer, in combination with carboplatin, in patients who are not candidates for curative surgery or radiation therapy.
"Non-small cell is the most common type of lung cancer, the leading cause of cancer death in the United States," said Dr. Mark A. Socinski, MD, Director, Lung Cancer Section, Division of Hematology/Oncology, University of Pittsburgh, and lead investigator of ABRAXANE phase II and phase III lung cancer trials.
"The FDA approval of ABRAXANE is exciting for healthcare professionals because it offers an important new treatment option for all types of non-small cell lung cancer patients, in an area that has seen few treatment advancements in recent years."
The ABRAXANE sNDA approval is based upon the results of CA-031, a phase III, multi-center, randomized open-label study where patients with advanced non-small cell lung cancer (NSCLC) received either ABRAXANE (100mg/m2) weekly plus carboplatin (AUC=6) every three weeks (n=521) or paclitaxel (200mg/m2) every three weeks plus carboplatin (AUC=6) (n=531).
The study met its primary end-point demonstrating astatistically significantly higher overall response rate for patients in the ABRAXANE arm compared to those in the paclitaxel arm (33pc vs 25pc ).
In the phase III study, ABRAXANE demonstrated a higher overall response rate as compared to paclitaxel for squamous cell carcinoma (41pc vs. 24pc ) and large cell carcinoma (33pc vs. 15pc ). ABRAXANE achieved a similar overall response rate to paclitaxel in patients with carcinoma/adenocarcinoma (26pc vs. 27pc ).
The most common adverse reactions ( and #8805;20pc ) of ABRAXANE in combination with carboplatin for NSCLC are anemia, neutropenia, thrombocytopenia, alopecia, peripheral neuropathy, nausea, and fatigue.
Additional regulatory submissions have been filed in Japan, Australia and New Zealand with anticipated decisions in 2013.
This approval marks the second indication for ABRAXANE in the United States. In the United States, ABRAXANE was first approved in 2005 for the treatment of metastatic breast cancer after failure of combination chemotherapy.
ABRAXANE for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension) is indicated for the treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy. Prior therapy should have included an anthracycline unless clinically contraindicated.
ABRAXANE is indicated for the first-line treatment of locally advanced or metastatic non-small cell lung cancer, in combination with carboplatin, in patients who are not candidates for curative surgery or radiation therapy.
Important Safety Information
WARNING - NEUTROPENIA
• Do not administer ABRAXANE therapy to patients who have baseline neutrophil counts of less than 1,500 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
• 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 < 1,500 cells/mm3
• 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
• Monitor for myelotoxicity by performing complete blood cell counts frequently, including prior to dosing on Day 1 for metastatic breast cancer (MBC) and Days 1, 8, and 15 for non-small cell lung cancer (NSCLC)
• Do not administer ABRAXANE to patients with baseline absolute neutrophil counts (ANC) of less than 1,500 cells/mm3
• In the case of severe neutropenia (<500 cells/mm3 for seven days or more) during a course of ABRAXANE therapy, reduce the dose of ABRAXANE in subsequent courses in patients with either MBC or NSCLC
• In patients with MBC, resume treatment with every-3 -week cycles of ABRAXANE after ANC recovers to a level >1,500 cells/mm3 and platelets recover to >100,000 cells/mm3
• In patients with NSCLC, resume treatment if recommended at permanently reduced doses for both weekly ABRAXANE and every-3-week carboplatin after ANC recovers to at least 1,500 cells/mm3 and platelet count of at least 100,000 cells/mm3 on Day 1 or to an ANC of at least 500 cells/mm3 and platelet count of at least 50,000 cells/mm3 on Days 8 or 15 of the cycle
. Sensory neuropathy is dose- and schedule-dependent
. The occurrence of Grade 1 or 2 sensory neuropathy does not generally require dose
modification . If and #8805; Grade 3 sensory neuropathy develops, treatment should be withheld until resolution to
Grade 1 or 2 for MBC or until resolution to and #8804; Grade 1 for NSCLC followed by a dose
reduction for all subsequent courses of ABRAXANE
• Severe and sometimes fatal hypersensitivity reactions, including anaphylactic reactions, have been reported
• Patients who experience a severe hypersensitivity reaction to ABRAXANE should not be re-challenged with this drug
. 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
. The starting dose should be reduced for patients with moderate or severe hepatic impairment
• 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
Use in Men
. Men should be advised not to father a child while receiving ABRAXANE
Randomized Metastatic Breast Cancer (MBC) Study
• The most common adverse reactions (>20pc ) with single-agent use of ABRAXANE in the MBC study were alopecia (90pc ), neutropenia (all cases 80pc ; severe 9pc ), sensory neuropathy (any symptoms 71pc ; severe 10pc ), abnormal ECG (all patients 60pc ; patients with normal baseline 35pc ), fatigue/asthenia (any 47pc ; severe 8pc ), myalgia/arthralgia (any 44pc ; severe 8pc ), AST elevation (any 39pc ), alkaline phosphatase elevation (any 36pc ), anemia (all cases 33pc ; severe 1pc ), nausea (any 30pc ; severe 3pc ), infections (24pc ), and diarrhea (any 27pc ; severe <1pc )
• Sensory neuropathy was the cause of ABRAXANE discontinuation in 7/229 (3pc ) patients
• Other adverse reactions of note included vomiting (any 18pc ; severe 4pc ), renal dysfunction (any 11pc ; severe 1pc ), fluid retention (any 10pc ; severe 0pc ); mucositis (any 7pc ; severe <1pc ), hepatic dysfunction (elevations in bilirubin 7pc ), hypersensitivity reactions (any 4pc ; severe 0pc ), thrombocytopenia (any 2pc ; severe <1pc ), and injection site reactions (<1pc ). In all ABRAXANE treated patients (n=366) ocular/visual disturbances were reported (any 13pc ; severe 1pc ). Dehydration and pyrexia were also reported
• Severe cardiovascular events possibly related to single-agent ABRAXANE occurred in approximately 3pc of patients and included cardiac ischemia/infarction, chest pain, cardiac arrest, supraventricular tachycardia, edema, thrombosis, pulmonary thromboembolism, pulmonary emboli, and hypertension
• Cases of cerebrovascular attacks (strokes) and transient ischemic attacks have been reported
Non-Small Cell Lung (NSCLC) Cancer Study
• Adverse reactions with a difference of >2pc , Grade 3 or higher, with combination use of ABRAXANE and carboplatin in NSCLC were: anemia (28pc ); neutropenia (47pc ); thrombocytopenia (18pc ), and peripheral neuropathy (3pc )
• The most common adverse reactions (> 20pc ) of ABRAXANE in combination with carboplatin for NSCLC were anemia, neutropenia, thrombocytopenia, alopecia, peripheral neuropathy, nausea, and fatigue
• The most common serious adverse reactions of ABRAXANE in combination with carboplatin for NSCLC were anemia (4pc ) and pneumonia (3pc )
• The most common adverse reactions resulting in permanent discontinuation of ABRAXANE were neutropenia (3pc ), thrombocytopenia (3pc ), and peripheral neuropathy (1pc )
• The most common adverse reactions resulting in dose reduction of ABRAXANE were neutropenia (24pc ), thrombocytopenia (13pc ), and anemia (6pc )
• The most common adverse reactions leading to withholding or delay in ABRAXANE dosing were neutropenia (41pc ), thrombocytopenia (30pc ), and anemia (16pc )
• The following common (> 10pc incidence) adverse reactions were observed at a similar incidence in ABRAXANE plus carboplatin-treated and paclitaxel injection plus carboplatin-treated patients: alopecia 56pc , nausea 27pc , fatigue 25pc , decreased appetite 17pc , asthenia 16pc , constipation 16pc , diarrhea 15pc , vomiting 12pc , dyspnea 12pc , and rash 10pc (incidence rates are for the ABRAXANE plus carboplatin treatment group)
Post-Marketing 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 to human albumin has not been studied . There have been reports of congestive heart failure and left ventricular dysfunction 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
. 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
• The safety and efficacy of ABRAXANE in pediatric patients have not been evaluated
• No toxicities occurred notably more frequently among patients > 65 years of age who received ABRAXANE for MBC
• Myelosuppression, peripheral neuropathy, and arthralgia were more frequent in patients >65 years of age treated with ABRAXANE and carboplatin in NSCLC
• The use of ABRAXANE has not been studied in patients with renal impairment
DOSAGE AND ADMINISTRATION
• Dose adjustment is recommended for patients with moderate and severe hepatic impairment and patients who experience severe neutropenia or severe sensory neuropathy during treatment with ABRAXANE
• Withhold ABRAXANE if AST >10 x ULN or bilirubin > 5 x ULN
• Dose reductions or discontinuation may be needed based on severe hematologic or neurologic toxicities
• Monitor patients closely
Non-small cell lung carcinoma (NSCLC) is any type of epithelial lung cancer other than small-cell lung carcinoma (SCLC). NSCLC is classified into two major types: squamous cell carcinoma, which accounts for 25-30pc of all NSCLC cases and non-squamous cell carcinoma, the most common lung cancer in the U.S.
When possible, lung cancer is primarily treated by surgical resection with curative intent. Chemotherapy may be used both pre-operatively (so-called "neoadjuvant chemotherapy") and post-operatively ("adjuvant chemotherapy") and as first-line for more advanced stages of lung cancer.
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.