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New Data Suggest Treatment Regimens That Include ABRAXANE May Be Active in Treating Metastatic Melanoma

– Data from Two Ongoing Studies Evaluating ABRAXANE in the Treatment of Metastatic Melanoma Presented at 45th Annual Meeting of the American Society of Clinical Oncology –

LOS ANGELES--(BUSINESS WIRE)--Jun 1, 2009 - Abraxis BioScience, Inc. (NASDAQ:ABII), a fully integrated biotechnology company, today announced results from two ongoing studies evaluating the chemotherapy agent ABRAXANE® for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension) (albumin-bound) for the treatment of a particularly hard-to-treat type of cancer, metastatic melanoma. In one study that evaluated ABRAXANE (150 mg/m2) given in combination with the targeted agent bevacizumab (10 mg/kg), 74 percent of patients were alive without their disease progressing four months after treatment, with a median progression-free survival (PFS) of 5.8 months. In addition, 91 percent of patients were alive six months after treatment with the ABRAXANE/bevacizumab combination and the one year survival rate was 68 percent. In a second study, previously untreated patients who received combination treatment with ABRAXANE (100 mg/m2) and the standard chemotherapy carboplatin (AUC 2) achieved a median overall survival of 11.1 months. Patients who received the same combination treatment with ABRAXANE but had received prior chemotherapy had an overall survival rate of 10.9 months. The findings were presented today at the 45th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Orlando, Fla.

“The current five-year survival rate for patients with advanced stage melanoma is 25 percent, making this one of the hardest cancers to treat.i These data show that new combinations using ABRAXANE may have anti-tumor activity in patients with metastatic melanoma, and suggest that further study of ABRAXANE for the treatment of metastatic melanoma is warranted,” said Jose Iglesias, MD, Chief Medical Officer and VP, Global Clinical Development of Abraxis Bioscience.

Melanoma is an aggressive form of skin cancer that affects more than 68,000 people in the U.S. each year. Melanoma is the leading cause of skin cancer death in the United States, killing more than 8,000 people annually.ii

About the Studies

I. Nab®-paclitaxel and bevacizumab as first-line therapy in patients with unresectable stage III and IV melanoma (Abstract #9061-Poster Presentation)

In this open-label, phase II study, 43 patients were treated with ABRAXANE 150 mg/m2 given on days one, eight and 15 and bevacizumab 10 mg/kg on days one and 15 of a 28-day treatment cycle (until disease progression or dose limiting toxicity). The primary endpoint of the study was progression-free survival at four months. Secondary endpoints included progression-free survival, overall survival, objective response rate, time to objective response, duration of objective response and safety and tolerability. Patients were eligible to participate in the study if they had been diagnosed with unresectable stage III or IV melanoma (more than 50 percent of patients in the study had stage IV disease) and received no prior chemotherapy treatment. Results of the study demonstrated:

 

  • PFS at four months of 74 percent (95% CI: 60%-88%)
  • Median PFS of 5.82 months (95% CI: 5.07-8.29)
  • Six month survival rate of 91 percent (95% CI: 81%-100%)
  • Twelve month survival rate of 68 percent (95% CI: 48%-87%)
  • An objective response rate of 29.7% was observed; one complete response (2.7%) and 10 partial responses (27%)
  • Forty-nine percent (n=18) of patients had stable disease for four weeks or longer
  • Thirty-four patients involved in the study are alive and nine patients have died to date

The median duration of follow-up for survival was 7.83 months and the median duration of survival has not been reached. Eligible patients also had an ECOG performance status of 0 or 1 and adequate organ function. Response assessments were made using RECIST criteria every two treatment cycles. Grade 3 toxicities occurred in 16 percent of patients and included: neutropenia, hand/foot syndrome, leucopenia, mucositis, neuropathy and proteinuria. No grade 4 events were observed.

“The early experience from this study suggests that ABRAXANE given in combination with bevacizumab may hold promise as a first-line therapy for patients with metastatic melanoma,” said Lynn E. Spitler, M.D., Director, Northern California Melanoma Center, St. Mary's Medical Center, San Francisco, CA. “The current study is ongoing and additional analysis will continue to explore the potential benefits of the ABRAXANE and bevacizumab combination in this hard-to-treat cancer.”

II. A phase II trial of carboplatin (C) and nab-paclitaxel (ABI-007-nab-P) in patients with unresectable stage IV melanoma: Final data from N057E1 (Abstract #9055-Poster Presentation) This was an open-label, phase II, two cohort study conducted in patients with unresectable stage IV melanoma who had received no prior chemotherapy treatment for their disease (the chemotherapy naïve cohort, n=39) or had received prior treatment (the previously treated cohort, n=34). The study included 73 patients who were treated with ABRAXANE (100 mg/m2) and carboplatin (AUC 2) on days one, eight, and 15 of a 28-day treatment cycle. A median of four cycles were administered in the study. Study results included:

For the chemotherapy naïve cohort (in which patients were followed for a minimum of 1.7 years):

  • Of the 39 patients enrolled: 10 (25.6 percent) confirmed responses (one complete response and nine partial responses)
  • Median PFS of 4.3 months
  • Median overall survival of 11.1 months

For the previously treated cohort (all but one patient was followed for a minimum of nine months):

  • Among the 34 patients enrolled: three (8.8 percent) confirmed responses (all partial responses)
  • Median PFS of 4.2 months
  • Median overall survival of 10.9 months
  • 11 patients remain on treatment with stable disease for at least four treatment cycles

The primary study objective was to assess tumor response rates (complete response plus partial response by RECIST criteria) in the chemotherapy naïve and previously treated cohorts. To be eligible for study participation, patients must have been older than 18, had an ECOG performance status less than or equal to 2 and had adequate organ function. Patients were not eligible if they had received prior treatment with a platinum or taxane agent, if they had peripheral neuropathy grade 2 or greater, had untreated brain metastases and were pregnant or nursing. The most common toxicities included neutropenia, thrombocytopenia, neuro-sensory, fatigue, nausea and vomiting.

An additional analysis showed that 83 percent (33/40) of patients who participated in the study tested positive for the tumor cell biomarker secreted protein acidic and rich in cysteine (SPARC). Median overall survival for SPARC positive patients was 12.8 months compared to 10.0 months for SPARC negative patients (p=0.021).

SPARC is an albumin-binding protein present in many types of cancer. SPARC is often found in the most aggressive metastatic tumor types, including breast, lung, prostate, melanoma, and pancreatic cancers, and clinical studies have shown that the presence of SPARC is often associated with a poor prognosis for patients.iii Recent research suggests a potential role for SPARC as a target for the development of anti-cancer agents.iv

Enrollment is ongoing for a phase III registration study comparing ABRAXANE to dacarbazine (or DTIC) in the treatment of stage IV chemotherapy naïve melanoma patients.

About ABRAXANE®

ABRAXANE is a solvent-free chemotherapy treatment option for metastatic breast cancer which was developed using Abraxis BioScience's proprietary nab® 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/mm3.

In the case of severe neutropenia (<500 cells>

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.

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 (ABRAXANE®), which is based on the company's proprietary tumor targeting technology known as the nab® 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. For more information about the company and its products, please visit www.abraxisbio.com.

i Korn, EL et al. Meta-Analysis of Phase II Cooperative Group Trials in Metastatic Stage IV Melanoma to Determine Progression-Free and Overall Survival Benchmarks for Future Phase II Trials. J Clin Oncol. 26:527-534 (2008).

ii American Cancer Society. Cancer Facts & Figures 2009. Atlanta: American Cancer Society; 2009. Available at http://www.cancer.org/docroot/STT/STT_0.asp.

iii Podhajcer et al. 2008. Cancer Metastasis Rev. 27, 691-705.

iv Neil Desai, Vuong Trieu, Bruno Damascelli, Patrick Soon-Shiong. SPARC Expression Correlates with Tumor Response to Albumin-Bound Paclitaxel in Head and Neck Cancer Patients. Translational Oncology. June 2009, Volume 2, Number 2, 59–64.

Contact: Abraxis BioScience, Inc.
Investors and Media Inquiries:
Maili Bergman, 310-881-1300
investorrelations@abraxisbio.com
or
Media Inquiries:
Victoria Fort, 202-361-0445
Victoria.Fort@zenogroup.com
 

Posted: June 2009

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