Results from a Phase 2 Study of ABRAXANE In Combination With Carboplatin Show Clinical Activity in the First Line Treatment of Patients with Advanced Non-Small Cell Lung Cancer

–Randomized pivotal Phase 3 study ongoing–


 

LOS ANGELES--(BUSINESS WIRE)--Aug 3, 2009 - Abraxis BioScience, Inc. (NASDAQ:ABII), an integrated, global biotechnology firm, reported that the results of a phase 2 study were presented today at the 13th Annual World Conference on Lung Cancer of the International Association for the Study of Lung Cancer (IASLC) in San Francisco, CA. The data presented provided evidence of anti-tumor activity in patients with advanced non-small cell lung cancer (NSCLC) receiving first- line treatment regimens of albumin-bound nab-paclitaxel (ABRAXANE® for Injectable Suspension) in combination with carboplatin. Clinical activity and safety indicators from this study led to the selection of weekly 100 mg/m2 ABRAXANE as an optimal dose. A Phase 3 randomized, multicenter study comparing carboplatin in combination with weekly 100 mg/m2 ABRAXANE or Taxol® injection is ongoing.


 

“The results from this phase 2 study show clinical activity that could offer promise in the treatment of this hard-to-treat cancer. Data from this phase 2 investigation across multiple dose and administration schedules of ABRAXANE led to the decision to initiate a phase 3 trial to further study ABRAXANE for the treatment of NSCLC. The Phase 3 trial is ongoing and includes 1,050 patients from 111 sites globally,” said José Iglesias, M.D., Chief Medical Officer and VP, Global Clinical Development of Abraxis Bioscience.


 

ABRAXANE was administered in escalating doses in combination with the standard chemotherapy agent carboplatin (AUC 6). Patients who received 100 mg/m2 ABRAXANE weekly had higher overall response rates (ORR) and progression-free survival (PFS) times compared with patients who received every three week and other weekly dosing regimens. Patients in the 100 mg/m2 weekly ABRAXANE group had a 48% ORR and PFS of 6.2 months. A retrospective histologic analysis, demonstrated that combination therapy with ABRAXANE and carboplatin shows anti-tumor activity against both squamous and nonsquamous NSCLC.


 

NSCLC is the most common form of lung cancer, accounting for approximately 85% of all lung cancer cases. The American Cancer Society (ACS) estimates that approximately 219,440 people will be diagnosed with lung cancer in the United States in 2009, and that approximately 159,000 deaths occur each year due to this cancer.i


 

About the Studies


 

I. Weekly and Every-3-Week nab-Paclitaxel Followed by Carboplatin as First-Line Therapy is Effective in Patients with Advanced Non-Small Cell Lung Cancer: Final Results of a Phase II Study (Abstract #PD3.4.1)


 

In this open-label, multicenter, phase II study, 175 patients were enrolled sequentially into seven cohorts and treated with escalating doses of ABRAXANE, administered either weekly or every three weeks in combination with carboplatin as follows:


 

 


 


  • ABRAXANE administered every three weeks in 225 mg/m2, 260 mg/ m2, 300 mg/ m2, and 340 mg/ m2 doses plus carboplatin (AUC 6) given every three weeks of a four week cycle (cohorts 1-4)
     
  • ABRAXANE 140 mg/m2 administered weekly for two weeks, followed by a week of rest plus carboplatin (AUC 6) every three weeks of a four week cycle (cohort 5)
     
  • ABRAXANE 100 mg/m2 and 125 mg/m2 administered weekly for three weeks plus carboplatin (AUC 6) every three weeks of a four week cycle (cohorts 6 and 7)
     


 

The primary endpoint of the study was percent of patients with confirmed complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), duration of response and overall survival (OS).


 

Results of the study are as follows:


 

 


 


  • The ORR was 56%, 48%, and 36% for the 140 mg/m2,100 mg/m2 and 125 mg/m2 weekly dose groups, respectively; and ranged from 24% to 40% for the every three week dose groups.
     
  • The most common grade 3/4 adverse event was neutropenia which occurred in 48% to 76% of patients across dose groups. Within the weekly dosing groups, the incidence of grade 4 neutropenia was 28%, 32% and 44% for the 100 mg/m2, 125 mg/m2 and 140 mg/m2 dose groups.
     
  • The incidence of grade 3 peripheral neuropathy ranged from 8% to 48% for all study groups and was lowest in the ABRAXANE 100 mg/m2 and 140 mg/m2 weekly dosing groups (both arms 8%). No grade 4 peripheral neuropathy was observed in any study group.
     
  • Based on the totality of the safety and clinical activity results across all treatment groups, the combination of ABRAXANE 100 mg/m2 weekly plus carboplatin AUC 6 every 21 days emerged as the optimal doublet.
     


 

“The early experience from this study suggests that ABRAXANE given in combination with carboplatin may hold promise as a first-line therapy for patients with advanced non-small cell lung cancer,” said Mark Socinski, M.D., University of North Carolina. “The current studies are ongoing and additional analyses will continue to explore the potential benefits of the ABRAXANE and carboplatin combination in this difficult to treat cancer.”


 

II. Retrospective Analysis of a Phase II Study of nab-Paclitaxel Plus Carboplatin in Advanced NSCLC (Abstract #PD3.3.4-Poster Presentation)


 

 


 


  • This was a retrospective histologic analysis of data from the above-referenced open label, multicenter, phase II study that was performed to assess whether clinical activity was observed in patients receiving nab-paclitaxel, regardless of histological subtype.
     


 

Results were analyzed across two major histological subtypes: squamous cell carcinoma and adenocarcinoma (nonsquamous cell carcinoma). This analysis demonstrated:


 

 


 


  • ABRAXANE in combination with carboplatin showed clinical activity in patients with NSCLC, regardless of histological subtype.
     
  • Patients with histologic confirmation of adenocarcinoma receiving weekly ABRAXANE demonstrated higher response rates compared with those receiving ABRAXANE on an every three week schedule (ORR: 59.4% versus 23.5 % respectively, P=0.003).
     
  • In patients with histological confirmation of squamous cell carcinoma receiving weekly vs. every three week dosing with ABRAXANE, the ORR was 39.0% and 35.6%, respectively.
     


 

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. ABRAXANE 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 and gastric.


 

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 Cancer Facts & Figures 2008. American Cancer Society publication. http://www.cancer.org/downloads/STT/500809web.pdf. Pg. 15,


 

 


 

Contact: Abraxis BioScience, Inc.

Maili Bergman

310-881-1300

investorrelations@abraxisbio.com

Investors and Media Inquiries

or

Victoria Fort

202-361-0445

Victoria.Fort@zenogroup.com

Media Inquiries


 

 

Posted: August 2009

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