(CHICAGO, IL) — Neither weekly nab-paclitaxel nor ixabepilone are superior to weekly paclitaxel in patients with chemotherapy-naïve advanced breast cancer receiving bevacizumab, results of an NCI-supported, cooperative group randomized Phase 3 study reported at the 2012 American Society of Clinical Oncology Annual Meeting.
”Weekly paclitaxel appears to offer better progression-free survival (PFS) than ixabepilone, and hematologic toxicity was greater with nab-paclitaxel,” said, Hope S. Rugo, MD, University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, who added that sensory neuropathy was greater in both experimental arms compared to paclitaxel.
Patients in the study had no prior chemotherapy for metastatic breast cancer and more than 12 months since adjuvant paclitaxel and measurable disease, Dr. Rugo said. Beginning in November 2008, 799 patients were randomized to the control arm, paclitaxel (90mg/m2; n=283), or one of two experimental regimens: nab-paclitaxel (150mg/m2; n=271) or ixabepilone (16mg/m2; n=245). Despite the study being amended following the recommendation that approval for bevacizumab in metastatic breast cancer be withdrawn; 98% of all patients also received bevacizumab.
The first interim analysis, performed after 165 events for progression-free survival (PFS) had been reached, revealed that compared to paclitaxel, ixabepilone crossed the futility boundary for superiority and on July 8, 2011, ixabepilone accrual was closed, Dr. Rugo said. A second interim analysis at 236 events for PFS found nab-paclitaxel crossed the futility boundary for superiority compared with paclitaxel and, on November 30, 2011, the study was closed.
Median follow-up for all surviving patients as of April 26, 2012, was 12 months; 99% of patients were female. By treatment arm, median PFS was 10.6 months for paclitaxel; 9.2 months for nab-paclitaxel; and 7.6 months for ixabepilone. PFS HR for nab-paclitaxel vs paclitaxel was 1.19 (P=0.12) and ixabepilone to paclitaxel, 1.53 (P<0.0001). An unplanned subset analysis of PFS showed no differences in the patients with ER+ or triple negative disease. Grade 3+ sensory neuropathy was 25% for nab-paclitaxel, 16% for ixabepilone, and 25% for paclitaxel.
With respect to interpretation of the study and next steps, these data suggest that similar patients should be treated with paclitaxel given on a weekly schedule; however, at this dose and schedule, there is no advantage associated with either nab-paclitaxel or ixabepilone. She noted that it is unlikely that the use of bevacizumab affected this comparison. Multiple correlative studies embedded in the trial design are ongoing.