Nab-Paclitaxel, Ixabepilone Not Superior to Paclitaxel

Chicago—A phase 3 study found that nab-paclitaxel and ixabepilone were not superior to standard treatment (paclitaxel) in patients with chemotherapy-naïve metastatic breast cancer who also received bevacizumab.

Hope S. Rugo, MD, professor of medicine and director of breast oncology and clinical trials education at the University of California, San Francisco, presented the results in an oral abstract session at the ASCO meeting. The National Cancer Institute supported the trial.

Median progression-free survival, the primary end point, was 10.6 months in the paclitaxel group, 9.2 months in the nab-paclitaxel group, and 7.6 months in the ixabepilone group. The difference between the paclitaxel and nab-paclitaxel groups was not significant (hazard ratio [HR], 1.19; 95% confidence interval [CI], 0.96-1.49; P=.12), but there was a significant difference when comparing the paclitaxel and ixabepilone groups (HR, 1.53; 95% CI, 1.24-1.90; P<.0001).

“At this dose and schedule, there is no advantage associated with either nab-paclitaxel or ixabepilone [compared with paclitaxel], and most toxicities are increased [with those drugs],” Dr. Rugo said.

Based on results of an earlier trial, the researchers used weekly paclitaxel with bevacizumab as the control arm. The study showed that adding bevacizumab to weekly paclitaxel improved response rates and progression-free survival in patients with chemotherapy-naïve metastatic breast cancer compared with paclitaxel alone.

In this trial, patients were randomized in a 1:1:1 ratio to receive weekly doses of 90 mg/m² of paclitaxel, 150 mg/m² of nab-paclitaxel, or 16 mg/m² of ixabepilone. Each group also received 10 mg/kg of bevacizumab every 2 weeks. Dr. Rugo said the drugs were given 3 out of every 4 weeks so that patients could recover from toxicity on the fourth week.

Inclusion criteria included no prior chemotherapy for advanced disease, ≥12 months from receiving adjuvant taxanes, peripheral neuropathy ≤ grade 1, and Eastern Cooperative Oncology Group Performance Status ≤ grade 1. Although men were allowed to enroll, 99% of patients were women.

In March 2011, the researchers amended the study to allow the optional use of bevacizumab after the FDA’s Oncologic Drugs Advisory Committee recommended withdrawing the approval for bevacizumab. Despite the amendment, 98% of patients received bevacizumab.

In July 2011, based on an interim analysis, the researchers stopped enrolling patients in the ixabepilone arm group; thus, the study became a 2-arm trial. The study ended in November 2011 when 799 patients had enrolled. In all, 283 patients were in the paclitaxel group, 271 patients were in the nab-paclitaxel group, and 245 were in the ixabepilone group. The median follow-up for the surviving patients was 12 months.

The time to treatment failure was 7.1 months in the paclitaxel group, 5.4 months in the nab-paclitaxel group, and 5.1 months in the ixabepilone group. The difference between the paclitaxel and nab-paclitaxel groups was significant (HR, 1.40; 95% CI, 1.16-1.70; P=.0005), as was the difference when comparing the paclitaxel and ixabepilone groups (HR, 1.37; 95% CI, 1.13-1.67; P=.0014).

Median overall survival was 26 months in the paclitaxel group, 27 months in the nab-paclitaxel group, and 21 months in the ixabepilone group. The differences between the groups were not significant.

There were significantly more hematologic and nonhematologic grade ≥3 adverse events (AEs) among patients taking nab-paclitaxel compared with patients taking paclitaxel. Compared with the paclitaxel group, the ixabepilone group had significantly fewer hematologic grade ≥3 AEs but significantly more nonhematologic grade ≥3 AEs.