Final Phase III data from clinical trial with Abraxane? (paclitaxel albumin-bound particles for injectable suspension developed by Celgene Biopharmaceuticals) in combination with carboplatin in patients with advanced non-small cell lung cancer (NSCLC)shows significantly improved overall response rate for patients receiving the drug combination.

The results were presented at the 47th annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Illinois.

Abraxane is a solvent-free chemotherapy treatment option for metastatic breast cancer which was developed using Celgene’s proprietary nab? technology platform. This protein-bound chemotherapy agent combines paclitaxel with albumin, a naturally-occurring human protein. The drugs is currently in various stages of investigation for the treatment of a variety of cancers including metastatic breast, non-small cell lung, malignant melanoma, pancreatic and gastric cancer.

Non-small cell lung carcinoma (NSCLC) is any type of epithelial lung cancer other than small-cell lung carcinoma (SCLC). As a class, NSCLCs are relatively insensitive to chemotherapy, compared to small-cell carcinoma. When possible, they are primarily treated by surgical resection with curative intent, although chemotherapy is increasingly being used both pre-operatively or neoadjuvant chemotherapy and post-operatively or adjuvant chemotherapy.

CA031 study design
In the study, patients were randomized to receive either Abraxane (100 mg/m2) every week without premedication plus carboplatin (AUC=6) every 3 weeks (n=521) or paclitaxel (200 mg/m2) every 3 weeks with premedication (n=531) plus carboplatin (AUC=6) as first-line therapy.

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Primary endpoint of overall response
As reported at ASCO 2010, the primary endpoint of overall response rate was 33% of patients in the Abraxane arm, compared to 25% in the paclitaxel arm (p=0.005). Histology subset analysis demonstrated an overall response rate of 41% vs. 24% (p<0.001) in patients with squamous histology (n=450) treated with Abraxane/carboplatin vs cremophor-based paclitaxel/carboplatin, however no difference in overall response rate was seen in the non-squamous patients (26% vs. 25%, n=602).

Median progression-free survival
For the intent-to-treat (ITT) population, the median progression-free survival (PFS) for patients in the Abraxane arm was 6.3 months, compared to 5.8 months in the paclitaxel arm (p=0.214, HR 0.902) Additionally, the median overall survival (OS) for patients in the Abraxane arm was 12.1 months, compared to 11.2 months in the paclitaxel arm (p=0.271, HR 0.922). In the ITT population, improvement was seen in PFS and OS endpoints favouring Abraxane, although this did not reach statistical significance.

In patients 70 years and older, those receiving Abraxane (n=74) achieved a median overall survival of 19.9 months, compared to 10.4 months for patients receiving cremaphor-based paclitaxel (n=82) (HR 0.583). This observation supports further investigation in the treatment of elderly NSCLC patients.

Squamous cell disease
Patients with squamous cell disease receiving Abraxane (n=229) achieved a median overall survival of 10.7 months, compared to 9.5 months for patients receiving cremaphor-based paclitaxel (n=221) (HR 0.890).

The most common grade 3 or higher adverse events in the Abraxane arm and paclitaxel arm, respectively, were neutropenia (42% vs. 48%, p=0.081), anemia (28% vs. 7%, p<0.001), thrombocytopenia (18% vs. 7%, p<0.001), leukopenia (14% vs. 13%, p=0.787), fatigue (7% vs. 9%, p=0.423) and sensory neuropathy (3% vs. 12% p<0.001).

Abraxane demonstrated lower rates of grade 3-4 neuropathy, despite 30% higher mean total paclitaxel being delivered (1514 vs. 1169 mg/m2).

First-line treatment in NSCLC
Based on these clinical results, and the agreement reached in the Special Protocol Assessment, Celgene is planning the submission of a sNDA for Abraxane for the first-line treatment of patients with advanced NSCLC.

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