Clinical Newswire, August 1, 2009-Weekly nab-paclitaxel treatment in patients with metastatic breast cancer (MBC) demonstrates significantly longer progression-free survival (PFS), in excess of 5 months, and less toxicity than docetaxel administered at the highest standard dose, a study published in the August 1, 2009 edition of the Journal of Clinical Oncology, has shown. The results suggest that weekly nab-paclitaxel may be an appropriate MBC treatment alternative to the current gold standard taxanes docetaxel and solvent-based paclitaxel (sb-paclitaxel).
In a previous trial, nab-paclitaxel, an albumin-bound form of paclitaxel, showed superior efficacy to sb-paclitaxel with less toxicity. The current study, led by William J. Gradishar of the Feinberg School of Medicine at Northwestern University in Chicago, Illinois, attempted to determine optimal dosing regimen and directly compare the efficacy of nab-paclitaxel to that of docetaxel.
Nab-paclitaxel is engineered using proprietary protein-bound nanoparticle technology to create tiny nanoparticles that are 100th the size of a red blood cell. In this form, the active chemotherapeutic drug, paclitaxel, can be delivered at a 50 percent higher dose over a 30 minute time period.
The study was an open-label randomized phase II trial of 300 patients with stage IV pathologically confirmed adenocarcinoma of the breast. Patients (mean age = 54.0 years) were randomly assigned to receive one of four treatment regimens: nab-paclitaxel given over 30 minutes at (a)300mg/m2 administered on day one of each 3 week cycle (q3w); b) 100mg/m2 administered weekly on days 1, 8 and 15 of each 4 week cycle, and c) 150mg/m2 administered on days 1, 8 and 15 of each 4 week cycle), or d) docetaxel (100mg/m2 q3w by intravenous infusion over 1 hour). Patient baseline characteristics were balanced across all treatment groups.
Primary end-point was overall response rate (ORR), defined as the percentage of patients with complete response (CR) and partial response (PR). Secondary end points included progression free survival (PFS), disease control rate (DCR, defined as >=16 weeks or confirmed overall PR or CR), duration of response, and patient survival. Assessments were made by both independent radiological review and by investigator evaluations using Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. Safety/tolerability was also determined.
By independent radiologist review, ORR was found to be higher for both 100mg/m2 (45%) and 150mg/m2 (49%) nab-paclitaxel groups compared to docetaxel (35%), however, the increase did not reach statistical significance. Statistical significance was reached by investigator assessment, however, for both 100mg/m2 (63%, P=0.002) and 150mg/m2 (74%, P<0.001) nab-paclitaxel groups compared to docetaxel (39%).
By both independent radiologist and investigator reviews, DCR was also found to be higher in patients treated with either weekly doses of nab-paclitaxel (75%-80%) compared with docetaxel (58%).
Weekly nab-paclitaxel at 150mg/m2 demonstrated significantly longer PFS than 100 mg/m2 docetaxel for both independent radiologist (median of 12.9 vs. 7.5 months; respectively, P=0.0065; HR, 0.495) and investigator (median of 14.6 vs. 7.8 months, respectively; P=0.012; HR,0.568) assessments.
Overall, nab-paclitaxel had a favorable safety and toxicity profile compared to docetaxel. Grade III and IV neutropenia, fatigue, and febrile neutropenia occurred more frequently and were more severe in the docetaxel group compared to the nab-paclitaxel groups, particularly grade IV neutropenia (75% vs. 5%-9%, respectively, P<0.001). The most common treatment related adverse events included alopecia, sensory neuropathy, neutropenia, fatigue and arthralgia. Sensory neuropathy resolved more rapidly after treatment with nab-paclitaxel (19-22 days) than with docetaxel (37 days).
The authors concluded that nab-paclitaxel demonstrates statistically and clinically superior efficacy over the highest standard dose of docetaxel, extending PFS in excess of 5 months in first line MBC patients. “This outcome may provide a significant advance in the armamentarium of treatment of patients with MBC in the first line setting”, the authors wrote.
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