Evidence update #1:
Updated results of the phase II study by Gradishar et al 2009 (see below) comparing weekly nab-paclitaxel (at two different doses) and three weekly docetaxel have demonstrated superiority for the weekly 150 mg/m2 nab-paclitaxel dose.r However, due to the increased toxicities associated with this dose it is the consensus of the reference committee to start at a dose of 100 mg/m2 for most patients.
Evidence update #2:
Whilst a significant number of patients in the CALGB40502/NCCTG N063H were treated in combination with bevacizumab, weekly nab-paclitaxel (at 150 mg/m2) was not superior to weekly paclitaxel at 90 mg/m2.r
The evidence supporting the use of nab-paclitaxel for the treatment of metastatic breast cancer is outlined in the three weekly nab-paclitaxel protocol (link to the evidence for Breast metastatic nab-paclitaxel three weekly protocol).
The weekly regimen for nab-paclitaxel was compared to the 3 weekly regimen in an open label, randomised, multicenter, phase II study. Between November 2005 and June 2006, a total of 300 patients were randomised to receive nab-paclitaxel 300 mg/m2 q3w (n=76), nab-paclitaxel 100 mg/m2 qw 3/4 (n=76), nab-paclitaxel 150 mg/m2 qw 3/4 (n=74), or docetaxel 100 mg/m2 q3w (n=74).r
The primary endpoints were overall response rate and safety and secondary endpoints were disease control rate, progression-free survival, duration of response and overall survival.r
When considering the use nab-paclitaxel, prescribers may wish to consider the results of the 799 patient phase III multicenter RCT CALGB 40502/NCCTG N063H reported at ASCO 2012 (Abstract CRA1002). The authors concluded that (at least in combination with bevacizumab), nab-paclitaxel 150 mg/m2 qw 3/4 was highly unlikely to be superior to paclitaxel 90 mg/m2 qw 3/4 for PFS, and that (in combination with bevacizumab), weekly paclitaxel was the better tolerated drug.r
On the basis of independent radiologist review, both 150 mg/m2 (49%) and 100 mg/m2 (45%) weekly of nab-paclitaxel demonstrated a higher overall response rate (ORR) than docetaxel (35%), but this did not reach statistical significance. This trend was supported by statistically significant investigator ORR for both weekly nab-paclitaxel doses versus docetaxel.r
A final overall survival analysis of this study was presented as a poster at the ASCO Breast Cancer Symposium in 2011. The overall survival in the 150 mg/m2 weekly nab-paclitaxel arm resulted in the longest overall survival (33.8 months) compared with the other nab-paclitaxel regimens or docetaxel.rr
|300 mg/m2 q3w
|100 mg/m2 qw
|150 mg/m2 qw
|100 mg/m2 q3w
||C vs D: 0.568
C vs B: 0.507
||C vs B:0.575
C vs D: 0.688
a = Overall p-value; b = Based on Cochran-Mantel-Haenszel test stratified by study center; c = Based on log-rank test.
Phase II trial of nab-paclitaxel compared with docetaxel as first line chemotherapy in patients with MBC: final analysis of OSr
© Clin Breast Cancer 2012
The most common treatment related adverse events were alopecia, sensory neuropathy, neutropenia, fatigue, and arthralgia. Neutropenia occurred more frequently and was more severe in patients who received docetaxel. In particular, grade 4 neutropenia was significantly higher in patients who received docetaxel (75%) compared with patients who received nab-paclitaxel 100 mg/m2 weekly, 150 mg/m2 weekly, or 300 mg/m2 q3w (5%, 5%, and 9%, respectively; P<0.001 for all three comparisons). Febrile neutropenia also occurred significantly more frequently in the docetaxel arm (8% v 1% in each nab-paclitaxel arm).r
Treatment-related toxicities r
© Journal of Clinical Oncology 2009