BOUDRY, Switzerland, Jun 02, 2012 (BUSINESS WIRE) -- --Response rate significantly improved in squamous-cell histology
--Trend toward overall survival demonstrated in squamous-cell compared to non-squamous-cell disease
--PDUFA date scheduled for Oct. 12, 2012
Celgene International Sarl, a subsidiary of Celgene Corporation today announced results from multiple presentations evaluating ABRAXANE(R) (paclitaxel protein-bound particles for injectable suspension) (albumin-bound) in combination with carboplatin in patients with advanced non-small cell lung cancer during the 48th American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Ill.
The two reports presented data from retrospective analyses of CA-031, the phase III, multi-center, randomized study where patients received either nab-paclitaxel (100mg/m(2)) weekly plus carboplatin (AUC=6) every three weeks (n=521) or paclitaxel (200mg/m(2)) every three weeks plus carboplatin (AUC=6) (n=531) as first-line therapy for advanced non-small cell lung cancer.
Based on the data from CA-031, Celgene submitted an sNDA for ABRAXANE(R) for the first-line treatment of patients with advanced non-small cell lung cancer with the U.S. Food and Drug Administration in December 2011. The current PDUFA date for the submission is Oct. 12, 2012.
Results of this study published ahead of print on April 30, 2012 in the Journal of Clinical Oncology demonstrated a higher overall response rate (ORR), the approved primary end-point of the study based on a Special Protocol Assessment (SPA), for patients in the nab-paclitaxel arm compared to those in the paclitaxel arm (33% vs. 25%, p=0.005).
The first sub-analysis evaluated elderly patients in the study (age greater-than or equal to 70, n=156) and patients under 70 (n=896). In both groups, ORR was higher in patients receiving nab-paclitaxel, though in elderly patients this difference was not significant. In elderly patients, progression-free survival (PFS) favored nab-paclitaxel (median 8.0 vs. 6.8 months, HR: 0.687, p=0.134) and overall survival was significantly improved (median 19.9 vs. 10.4 months, HR 0.583, p=0.009). For patients under 70, there was no significant difference in PFS or OS between the arms of the study.
In elderly patients, less grade 3/4 neutropenia (54% vs. 74%) and neuropathy (7% vs. 23%) and increased thrombocytopenia (23% vs. 14%) and anemia (23% vs. 10%) in the nab-paclitaxel arm vs. the paclitaxel arm.
The second report evaluated patients with squamous-cell histology (n=450) and non-squamous cell patients (n=602).
In squamous-cell histology patients, the nab-paclitaxel arm demonstrated a significantly higher ORR (41% vs. 24%, p<0.001), similar PFS (5.6 vs. 5.7 months, HR: 0.865) and a slight improvement in OS (10.7 vs. 9.5 months, HR:0.890), compared to the paclitaxel arm. Non-squamous-cell histologies including adenocarcinoma (ADENO), large-cell carcinoma (LC) and not otherwise specified (NOS) were characterized individually for ORR. In these histologies, the ORR in patients receiving nab-paclitaxel compared to paclitaxel was the nab-paclitaxel arm, respectively, was 26% vs. 27% in ADENO, 33% vs. 15% in LC and 24% vs. 15% in NOS. PFS in non-squamous cell histology patients who received nab-paclitaxel compared to those who received paclitaxel, respectively, was 6.9 vs. 6.5 months (hr:0.933)(hr:p=0.532). By histology, median PFS measures for nab-paclitaxel patients compared to paclitaxel patients, respectively, were 6.9 vs. 6.9 months in ADENO, NR (not reached) vs. 3.8 months in LC and 6.4 vs. 4.3 months in NOS. OS by histology for patients receiving nab-paclitaxel compared to those receiving paclitaxel, respectively was 13.9 vs. 13.6 months in ADENO, 12.4 vs. 10.6 months in LC and 10.4 vs. 11.2 months in NOS.
In squamous-cell histology patients, nab-paclitaxel demonstrated produced lower rates of grade 3/4 neuropathy (3% vs. 11%) and neutropenia (43% vs. 51%), and higher rates of anemia (27% vs. 4%) and thrombocytopenia (21% vs. 7%) compared to paclitaxel. In non-squamous-cell histology patients, patients receiving nab-paclitaxel versus paclitaxel, respectively demonstrated lower rates of grade 3/4 neuropathy (3% vs. 12%) and neutropenia (50% vs. 63%), and higher rates of anemia (28% vs. 9%) and thrombocytopenia (16% vs. 11%).
These results are from an investigational study. ABRAXANE is not indicated for the treatment of non-small cell lung cancer.
ABRAXANE(R) 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.
Important Safety Information
WARNING - NEUTROPENIA
-- ABRAXANE therapy should not be administered to patients with metastatic breast cancer who have baseline neutrophil counts of less than 1,500 cells/mm(3). 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.
-- ABRAXANE should not be used in patients who have baseline neutrophils counts of < 1,500 cells/mm(3)
-- Patients who experience a severe hypersensitivity reaction to ABRAXANE should not be rechallenged with the drug
WARNINGS AND PRECAUTIONS
-- Bone marrow suppression (primarily neutropenia) is dose dependent and a dose limiting toxicity
-- In order to monitor the occurrence of myelotoxicity, perform frequent peripheral blood cell counts
-- Retreat with subsequent cycles of ABRAXANE after neutrophils recover to a level >1,500 cells/mm(3) and platelets recover to >100,000 cells/mm(3)
-- In the case of severe neutropenia (<500 cells/mm(3) for 7 days or more), during a course of ABRAXANE therapy, dose reduce for subsequent courses of therapy
-- Sensory neuropathy occurs frequently with ABRAXANE
-- The occurrence of grade 1 or 2 sensory neuropathy does not generally require dose modification
-- If grade 3 sensory neuropathy develops, treatment should be withheld until resolution to grade 1 or 2 followed by a dose reduction for all subsequent courses of ABRAXANE
-- 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 and 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
-- There are no adequate and well-controlled studies in pregnant women receiving ABRAXANE
-- 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 to not father a child while receiving ABRAXANE
ADVERSE REACTIONS - Randomized Metastatic Breast Cancer Study
-- Severe cardiovascular events possibly related to single-agent ABRAXANE occurred in approximately 3% of patients. These events 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
-- In the randomized metastatic breast cancer study, the most common adverse events (greater-than or equal to 20%) were alopecia (90%), neutropenia (all cases 80%; severe 9%), sensory neuropathy (any symptoms 71%; severe 10%), abnormal ECG (all patients 60%, patients with normal baseline 35%), asthenia (any 47%; severe 8%), myalgia/arthralgia (any 44%; severe 8%), AST (SGOT) elevations (any 39%), alkaline phosphatase elevations (any 36%), anemia (all cases 33%; severe 1%), nausea (any 30%; severe 3%), diarrhea (any 27%; severe <1%) and infections (24%). Other adverse events of note include vomiting (any 18%; severe 4%), and mucositis (any 7%; severe <1%). 3% (7 of 229) of patients discontinued the use of ABRAXANE due to sensory neuropathy.
-- Other adverse events have included ocular/visual disturbances (any 13%; severe 1%), renal dysfunction (any 11%; severe 1%), fluid retention (any 10%; severe 0%), hepatic dysfunction (elevations in bilirubin 7%), hypersensitivity reactions (any 4%; severe 0%), cardiovascular reactions (severe 3%), thrombocytopenia (any 2%; severe <1%), and injection site reactions (<1%). Dehydration and pyrexia were also reported.
Post-Marketing Experience with ABRAXANE and other Paclitaxel Formulations
-- Severe hypersensitivity reactions have also been reported with ABRAXANE
-- During postmarketing surveillance, reports of congestive heart failure and left ventricular dysfunction were observed, primarily among individuals with underlying cardiac history or prior exposure to cardiotoxic drugs like anthracyclines
-- 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
-- No drug interaction studies have been conducted with ABRAXANE
-- Caution should be exercised when administering ABRAXANE concomitantly with medicines known to inhibit or induce either CYP2C8 or CYP3A4
USE IN SPECIFIC POPULATIONS
-- 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 greater-than or equal to 65 years of age who received ABRAXANE
-- The use of ABRAXANE has not been studied in patients with renal impairment
-- Patients were excluded for baseline serum bilirubin >1.5 mg/dL or baseline serum creatinine > 2 mg/dL
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
Please see full Prescribing Information, including Boxed WARNING, CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS, and ADVERSE REACTIONS.
About Celgene International Sarl
Celgene International Sarl, located in Boudry, in the Canton of Neuchatel, Switzerland, is a wholly owned subsidiary and international headquarters of Celgene Corporation. 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 the Company's website at www.celgene.com .
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. We undertake 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 our Annual Report on Form 10-K and our other reports filed with the Securities and Exchange Commission.
SOURCE: Celgene Corporation