Better Outcome With Paclitaxel vs Nab-Paclitaxel or Ixabepilone Plus Bevacizumab in First-Line Treatment of Advanced Breast Cancer


Key Points

  • Ixabepilone was inferior to paclitaxel in progression-free survival, and nab-paclitaxel was not superior to paclitaxel, with a trend toward inferiority.
  • Toxicity was greater with nab-paclitaxel vs paclitaxel.

In the phase III CALGB 40502/NCCTG N063H/Alliance trial reported in the Journal of Clinical Oncology, Rugo et al found that outcomes in first-line treatment for advanced breast cancer were better with weekly paclitaxel plus bevacizumab (Avastin) compared with weekly nanoparticle albumin-bound (nab)-paclitaxel (Abraxane) or ixabepilone (Ixempra) plus bevacizumab.

Study Details

In the trial, 799 patients with stage IIIC or IV disease were randomly assigned 1:1:1 to bevacizumab plus paclitaxel at 90 mg/m2 (n = 283), nab-paclitaxel at 150 mg/m2 (n = 271), or ixabepilone at 16 mg/m2 (n = 245) once per week for 3 of 4 weeks. The study was activated in October 2008 and was closed to accrual in November 2011. In March 2011, a protocol amendment made bevacizumab use optional at the time of randomization; in total, 93% of patients received bevacizumab (10 mg/kg on days 1 and 15 of each cycle). The primary endpoint was progression-free survival.


The ixabepilone arm was closed for futility on first interim analysis (July 2011), and the nab-paclitaxel arm was closed for futility on second interim analysis (November 2011).

Median progression-free survival was 11.0 months in the paclitaxel group vs 7.4 months in the ixabepilone group (hazard ratio [HR] = 1.59, P < .001) and 9.3 months in the nab-paclitaxel group (HR = 1.20, P = .054). Median time to treatment failure was 6.6 months vs 5.2 months (P < .001) and 4.9 months (P < .001). Median overall survival was 27.4 months vs 23.6 months in the paclitaxel vs ixabepilone comparison (HR = 1.31, P = .027) and 26.5 months vs 23.5 months in the paclitaxel vs nab-paclitaxel comparison (HR = 1.17, P = .20).

Adverse Events

Adverse events of grade ≥ 3 occurred in 60% of the paclitaxel group, 84% of the nab-paclitaxel group (P < .001), and 61% of the ixabepilone group. Hematologic adverse events of any grade occurred in 22%, 55% (P < .001), and 12% (P = .0037). Nonhematologic adverse events of any grade occurred in 49%, 65% (P < .001), and 58%. Grade ≥ 2 sensory neuropathy was more common with nab-paclitaxel vs paclitaxel (54% vs 46%, P = .031) and was associated with more frequent and earlier dose reductions.

The investigators concluded: “In patients with chemotherapy-naive advanced [breast cancer], ixabepilone once per week was inferior to paclitaxel, and nab-paclitaxel was not superior with a trend toward inferiority. Toxicity was increased in the experimental arms, particularly for nab-paclitaxel. Paclitaxel once per week remains the preferred palliative chemotherapy in this setting.”

Hope S. Rugo, MD, of the University of California at San Francisco Helen Diller Family Comprehensive Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.

The study was supported in part by grants from the National Cancer Institute. For full disclosures of the study authors, visit

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