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Abstract:
Weekly ABRAXANE Demonstrated Significantly Longer Progression-free Survival Compared with Docetaxel Administered Every Three Weeks as First-line Therapy in Patients with Metastatic Breast Cancer

New Study Results Published Compare ABRAXANEŽ to TaxotereŽ

Los Angeles, CA | Posted on May 27th, 2009

Abraxis BioScience Inc. (NASDAQ:ABII) announced today that final results from an open-label Phase II study evaluating three dose levels of the company's chemotherapy agent ABRAXANEŽ for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension) (albumin bound) compared to the highest standard dose of Taxotere (docetaxel) Injection Concentrate, in the first-line treatment of patients with metastatic breast cancer were published in the Journal of Clinical Oncology. According to investigator-assessed results, ABRAXANE administered weekly at 150 mg/m2 demonstrated an increase in progression-free survival (PFS) over docetaxel of 14.6 months versus 7.8 months, respectively (p=0.012). Results from the independent assessment of PFS for the 150mg/m2 treatment arm also demonstrated an increase in PFS (12.9 versus 7.5 months, respectively; p=0.0065). Investigators also noted a trend toward improvement in the study's primary endpoint, overall response rate (ORR), confirmed complete and partial responses by Response Evaluation Criteria in Solid Tumors (RECIST) criteria with weekly ABRAXANE. In investigator-assessed results, the ORR was 74 percent for ABRAXANE 150 mg/m2 weekly arm (p<0.001) and 63 percent for the weekly ABRAXANE 100 mg/m2 treatment arm (p=0.02), compared to a response rate of 39 percent for patients treated with docetaxel. However, improved ORR did not reach statistical significance in an independent radiological review of the data. Patients treated with weekly 150 mg/m2 ABRAXANE also experienced a higher disease control rate of 91 percent vs. 69 percent for the docetaxel arm (p=0.005), as measured by RECIST-defined stable disease (≥ 16 weeks) or confirmed partial or complete response. Additionally, patients treated with ABRAXANE experienced less overall toxicity than the docetaxel arm.

"The nearly double progression-free survival advantage demonstrated in this study is encouraging and supports the growing body of evidence exploring ABRAXANE's role in the treatment of metastatic breast cancer," said William Gradishar, M.D., F.A.C.P., Director, Breast Medical Oncology at Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, co-lead investigator of the study. "The results of this study demonstrate that ABRAXANE, when given weekly at a dose of 150mg/m2, may be more effective and better tolerated than solvent-based docetaxel."

"These results further increase our understanding of the role of ABRAXANE in treating patients with metastatic breast cancer," commented Lonnie Moulder, President and Chief Executive Officer, Abraxis BioScience Inc. "As we expand globally to bring important therapies to patients, we look forward to continuing to explore ABRAXANE's potential in ongoing clinical studies."

ABRAXANE is currently approved for the treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within six months of adjuvant chemotherapy. Prior therapy should have included an anthracycline unless clinically contraindicated.

The results from this study have not been formally reviewed by the Food and Drug Administration.

About the Study

This Phase II, open-label, randomized clinical study was designed to evaluate the safety and efficacy of three doses of ABRAXANE against the highest standard dose of docetaxel. The study involved 300 patients with previously untreated metastatic (stage 4) breast cancer who were randomized to four treatment arms: ABRAXANE 150 mg/m2 administered every week (n=74); ABRAXANE 100 mg/m2 administered every week (n=76); ABRAXANE 300 mg/m2 administered once every three weeks (n=76); and docetaxel injection 100 mg/m2 administered once every three weeks (n=74). Results were assessed by both study investigators and an independent radiology review of radiological data.

The primary study endpoint was overall response rate (ORR), defined as the percentage of patients that achieved an objective confirmed overall complete or partial response (CR or PR, respectively) based on RECIST guidelines. Secondary efficacy endpoints included disease control rate (DCR; stable disease for ≥16 weeks, or confirmed overall PR or CR), progression-free survival (PFS; defined as the time from date of randomization to the start of disease progression or death), duration of response (measured as PFS for patients who achieved confirmed CR or PR) and patient survival. The safety and tolerability study endpoints included the incidence of treatment-emergent and treatment-related adverse events (TRAEs) and serious adverse events.

Progression Free Survival

ABRAXANE 150 mg/m2 administered weekly demonstrated a statistically and clinically significant longer median PFS compared with docetaxel injection for both the investigator (14.6 versus 7.8 months, respectively; p=0.012) and independent radiologist (12.9 versus 7.5 months, respectively; p=0.0065) assessed results. Weekly ABRAXANE 100mg/m2 also prolonged median PFS as assessed by the independent radiologist review (12.8 versus 7.5 months, respectively; p=0.0498), but this result was not confirmed by the investigator assessment. ABRAXANE administered 300 mg/m2 every three weeks increased median PFS compared with docetaxel for both the independent radiologist (median, 11.0 versus 7.5 months, respectively) and investigator (median, 10.9 versus 7.8 months, respectively) assessed results, but did not meet statistical significance.

Response Rate

Based on independent radiologist review, the ORR for the 150 mg/m2 and 100 mg/m2 dose arms and docetaxel were 49 percent, 45 percent, and 35 percent respectively. Investigator assessments of the ORR were higher for the weekly ABRAXANE arms versus docetaxel injection with rates of: 74 percent for the 150 mg/m2 ABRAXANE arm (p<0.001); 63 percent for the 100 mg/m2 arm (p=0.002); and 39 percent for docetaxel.

Disease Control

Based on both the investigator reviews and independent radiologist, the DCR was significantly higher for patients receiving 150 mg/m2 weekly ABRAXANE compared with docetaxel. The investigator-assessed DCR for the weekly 150 mg/m2 arm was 91 percent (p=0.005) and the DCR for the weekly 100 mg/m2 arm was 83 percent (p=0.009). These results were confirmed in the independent radiologist assessment with a statistically significant comparison for both the weekly ABRAXANE 150 mg/m2 (80 percent, p=0.017) and 100 mg/m2 (75 percent, p=0.009) compared to docetaxel injection (58 percent).

Tolerability

The published study reported that the weekly ABRAXANE treatment arms overall demonstrated a favorable safety and tolerability profile compared with docetaxel. Patients treated with ABRAXANE experienced less frequent grade 3/4 treatment-related adverse events including neutropenia, febrile neutropenia and fatigue. The rate of grade 4 neutropenia was 75 percent for patients treated with Taxotere compared to a rate of 5 percent for patients treated with weekly ABRAXANE 150 mg/m2 and 100 mg/m2. Febrile neutropenia also occurred more frequently in patients receiving Taxotere (eight percent versus one percent in each ABRAXANE treatment arm). The incidence of sensory neuropathy was comparable between the weekly ABRAXANE doses and Taxotere, however sensory neuropathy resolved more rapidly after treatment with ABRAXANE. In particular, the median time to improvement in grade 3 sensory neuropathy (to ≤ grade 1) was 22, 22, and 19 days, respectively, for patients who received ABRAXANE 300 mg/m2 q3w, 100 mg/m2 weekly, and 150 mg/m2 weekly compared with 37 days for patients who received docetaxel 100 mg/m2 q3w. Fatigue was more common and more severe in the Taxotere arm (19 percent of patients experienced grade 3/4 fatigue in the Taxotere arm compared to five percent for the ABRAXANE 300 mg/ m2 arm, zero percent for the ABRAXANE 100 mg/m2 arm and three percent on the ABRAXANE 150 mg/m2 arm). Incidences of arthralgia (grade 1/2) were comparable between patients who received Taxotere or weekly ABRAXANE 100 mg/m2 (22 percent and 19 percent, respectively). Thirty-two percent of patients reported arthralgia of any grade on the 300 mg/m2 ABRAXANE arm and 35 percent experienced arthralgia on the ABRAXANE 150 mg/m2 arm.

About Metastatic Breast Cancer

Breast cancer is a disease that will affect one in eight women during her lifetime.i Metastatic breast cancer is defined as the spread of a malignant tumor from its original site (the breast) to other parts of the body.ii It is estimated that nearly 155,000 women in the U.S. are currently living with metastatic breast cancer and this number is projected to increase to nearly 162,000 by the year 2011.iii Nearly all breast cancer deaths are attributable to advanced or metastatic breast cancer, and it is estimated that every 13 minutes a woman dies from the disease.iv However, more women are surviving breast cancer than ever beforev; the current five-year survival rate for women with metastatic breast cancer is 27 percent.vi

About ABRAXANEŽ

ABRAXANE is a solvent-free chemotherapy treatment option for metastatic breast cancer which was developed using Abraxis BioScience's proprietary nabŽ technology platform. This protein-bound chemotherapy agent combines paclitaxel with albumin, a naturally-occurring human protein. By wrapping the albumin around the active drug, ABRAXANE can be administered to patients at higher doses, delivering higher concentrations of paclitaxel to the tumor site than solvent-based paclitaxel. Nab-paclitaxel is currently in various stages of investigation for the treatment of the following cancers: expanded applications for metastatic breast, non-small cell lung, malignant melanoma, pancreatic, gastric and head and neck.

The U.S. Food and Drug Administration approved ABRAXANE for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension) (albumin-bound) in January 2005 for the treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within six months of adjuvant chemotherapy. Prior therapy should have included an anthracycline unless clinically contraindicated. For the full prescribing information for ABRAXANE please visit www.abraxane.com.

IMPORTANT SAFETY INFORMATION

The use of ABRAXANE has not been studied in patients with hepatic or renal dysfunction. In the randomized controlled trial, patients were excluded for baseline serum bilirubin >1.5 mg/dL or baseline serum creatinine >2 mg/dL.

ABRAXANE can cause fetal harm when administered to a pregnant woman. Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment with ABRAXANE.

Men should be advised to not father a child while receiving treatment with ABRAXANE. It is recommended that nursing be discontinued when receiving ABRAXANE therapy. ABRAXANE contains albumin (human), a derivative of human blood.

Caution should be exercised when administering ABRAXANE concomitantly with known substrates or inhibitors of CYP2C8 and CYP3A4.

ABRAXANE therapy should not be administered to patients with metastatic breast cancer who have baseline neutrophil counts of less than 1,500 cells/mm3. It is recommended that frequent peripheral blood cell counts be performed on all patients receiving ABRAXANE. Patients should not be retreated with subsequent cycles of ABRAXANE until neutrophils recover to a level >1,500 cells/mm3 and platelets recover to a level >100,000 cells/mm3In the case of severe neutropenia (<500 cells/mm3for 7 days or more) during a course of ABRAXANE therapy, a dose reduction for subsequent courses is recommended. Sensory neuropathy occurs frequently with ABRAXANE.

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. Severe cardiovascular events possibly related to single-agent ABRAXANE occurred in approximately 3% of patients in the randomized trial. These events included chest pain, cardiac arrest, supraventricular tachycardia, edema, thrombosis, pulmonary thromboembolism, pulmonary embolism, and hypertension.

In the randomized metastatic breast cancer study, the most important adverse events included alopecia (90%), neutropenia (all cases 80%; severe 9%), sensory neuropathy (any symptoms 71%; severe 10%), asthenia (any 47%; severe 8%), myalgia/arthralgia (any 44%; severe 8%), anemia (all 33%; severe 1%), infections (24%), nausea (any 30%; severe 3%), vomiting (any 18%; severe 4%), diarrhea (any 27%; severe <1%), and mucositis (any 7%; severe <1%).

Other adverse reactions have included ocular/visual disturbances (any 13%; severe 1%), fluid retention (any 10%; severe 0%), hepatic dysfunction (elevations in bilirubin 7%, alkaline phosphatase 36%, AST [SGOT] 39%), renal dysfunction (any 11%; severe 1%), thrombocytopenia (any 2%; severe <1%), hypersensitivity reactions (any 4%; severe 0%), cardiovascular reactions (severe 3%), and injection site reactions (<1%). During postmarketing surveillance, rare occurrences of severe hypersensitivity reactions have been reported with ABRAXANE.

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About Abraxis BioScience Inc.
Abraxis BioScience is a fully integrated global biotechnology company dedicated to the discovery, development and delivery of next-generation therapeutics and core technologies that offer patients safer and more effective treatments for cancer and other critical illnesses. The company's portfolio includes the world's first and only protein-bound nanoparticle chemotherapeutic compound (ABRAXANEŽ), which is based on the company's proprietary tumor targeting technology known as the nabŽ platform. The first FDA approved product to use this nab platform, ABRAXANE, was launched in 2005 for the treatment of metastatic breast cancer and is now approved in 36 countries. The company continues to expand the nab platform through a robust clinical program and deep product pipeline. Abraxis trades on the NASDAQ Global Market under the symbol ABII.

i Detailed Guide: Breast Cancer What Are the Key Statistics for Breast Cancer? American Cancer Society. www.cancer.org/docroot/CRI/content/CRI_2_4_1X_What_are_the_key_statistics_for_breast_cancer_5.asp.

ii Detailed Guide: Advanced Cancer What Is Metastatic Cancer? American Cancer Society. www.cancer.org/docroot/CRI/content/CRI_2_4_1x_What_Is_Metastatic_Cancer.asp?sitearea=.

iii Data on file. DA-ABR-03, Abraxis Bioscience, Inc

iv ACS Cancer Facts & Figures 2008

v Ries LAG, Melbert D, Krapcho M, et al., eds. SEER Cancer Statistics Review, 1975-2004, National Cancer Institute. Bethesda, MD, Available online.

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