The Food and Drug Administration has approved the albumin-bound formulation of paclitaxel for injectible suspension as first-line treatment of locally advanced or metastatic non–small cell lung cancer, the agency announced on Oct. 12.
Marketed as Abraxane, nanoparticle albumin-bound (nab)-paclitaxel was developed as an alternative to Taxol, which delivers paclitaxel in a highly toxic cremophor solvent. The FDA said it based the new approval on the previous approval of Taxol for this indication and a supportive study.
Abraxis Bioscience, a subsidiary of Celgene Corp., markets Abraxane. Nab-paclitaxel was initially approved in 2005 as a treatment for breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy.
The new indication is for use in combination with carboplatin for the initial treatment of patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) who are not candidates for curative surgery or radiation therapy. The recommended dose and schedule is 100 mg/m2 administered as an intravenous infusion over 30 minutes on days 1, 8, and 15 of each 21-day cycle. The recommended dose of carboplatin is AUC = 6 mg/min per mL on day 1 of each 21-day cycle after the Abraxane infusion is completed.
Approval was based on the previous approval of Taxol injection for the same indication, plus a randomized open-label, multinational study "establishing that Abraxane was as at least as active (as determined by overall response rate) as paclitaxel when both agents are used in combination with carboplatin," the FDA said.
In the study – the CA-031 trial – 521 patients with locally advanced or metastatic NSCLC were treated with Abraxane (at a dose of 100 mg/m2 as a weekly infusion) and 531 were treated with paclitaxel injection (at a dose of 200 mg/m2 as an IV infusion 3 three weeks). All patients received the same dose and schedule of carboplatin every 3 weeks.
Premedication with corticosteroids and an antihistamine was used in all patients receiving paclitaxel, but use was discretionary in the Abraxane arm.
The primary end point of the study, the overall response rate (the proportion of patients who achieved a durable complete or partial response, as determined by blinded radiological reviewers), was 33% among those in the Abraxane arm, compared with 25% of those in the paclitaxel arm, a statistically significant difference.
Among the responders in both groups, the durability of the responses was statistically similar, with median response duration reaching 6.9 months among those on Abraxane and 6.0 months among those on paclitaxel. There was no significant difference in overall survival between the two groups.
Celgene noted in a written statement that Abraxane demonstrated a higher overall response rate for squamous cell carcinoma (41% vs. 24%) and large cell carcinoma (33% vs. 15%) but was similar in patients with carcinoma/adenocarcinoma (26% vs. 27%).
The rate of serious adverse reactions was 18% in both groups: anemia (4%) and thrombocytopenia (3%) were the most common serious adverse reactions reported among those on Abraxane, according to the FDA. The safety evaluation was based on 1,038 patients who received at least one dose of their planned treatments.
The Abraxane label carries a neutropenia warning that it should not be administered in patients with baseline neutrophil counts of less than 1,500 cells/mm3, and that frequent peripheral blood cell counts should be performed to monitor occurrence of bone marrow suppression. The agency also warns that Abraxane should not be substituted "for or with other paclitaxel formulations."
Abraxane is currently being studied for the treatment of pancreatic, metastatic melanoma, bladder, and ovarian cancers, and for expanded applications for breast cancer, according to Celgene.