Phase III Data: Abraxane (Paclitaxel) Improves Survival in Metastatic Melanoma
Drug is approved for breast cancer and NSCLC in U.S. (Oct. 25)
Results have been reported from a phase III, randomized, open-label, international study (CA033) of Abraxane (paclitaxel protein [albumin]-bound particles for injectable suspension) in chemotherapy-naïve patients with metastatic melanoma.
The study showed a statistically significant improvement in progression-free survival (PFS) in patients treated with Abraxane compared with patients receiving dacarbazine chemotherapy (4.8 vs. 2.5 months, respectively; P = 0.044). An interim analysis of overall survival (OS) — the study’s secondary endpoint — showed a trend in favor of Abraxane compared with dacarbazine (12.8 vs. 10.7 months, respectively; P = 0.094).
The safety profile of Abraxane was comparable with other pivotal clinical trials of the drug. The most common grade-3 or greater, treatment-related adverse events were neuropathy (Abraxane: 25% vs. dacarbazine: 0%) and neutropenia (Abraxane: 20% vs. dacarbazine: 10%). The median time to the improvement of neuropathy with Abraxane was 28 days.
The study results will be presented at the Society for Melanoma Research 2012 Congress on November 11 in Hollywood, California.
The CA033 trial was an investigational study. Abraxane is not approved for the treatment of metastatic melanoma in the U.S.
CA033 was a phase III randomized, open-label, international trial that evaluated the safety and efficacy of Abraxane versus standard chemotherapy (dacarbazine) in chemotherapy-naïve patients with stage IV metastatic melanoma. Most of the patients were men (66%); most had an Eastern Cooperative Oncology Group (ECOG) status of 0 (71%); and most had advanced metastatic disease (M1c stage: 65%). Dacarbazine is the only chemotherapy approved since 1975 by the FDA for the treatment of metastatic melanoma.
In the CA033 study, 529 chemotherapy-naïve patients were randomly assigned to receive either Abraxane (150 mg/m2 weekly for 3 out of 4 weeks; n = 264) or standard chemotherapy with dacarbazine (1,000 mg/m2 every 3 weeks; n = 265). The primary endpoint was PFS, based on blinded assessments of CT scans obtained every 8 weeks, evaluated per RECIST criteria. The secondary endpoint was OS, and other endpoints included the objective response rate, the disease control rate, and safety/tolerability.
Abraxane was first approved in the U.S. in January 2005 for the treatment of breast cancer after the failure of combination chemotherapy for metastatic disease or after relapse within 6 months of adjuvant chemotherapy. In October 2012, Abraxane was also approved for the first-line treatment of locally advanced or metastatic non–small-cell lung cancer (NSCLC), in combination with carboplatin, in patients who are not candidates for curative surgery or radiation therapy.
Source: Celgene, October 25, 2012.