Randomized phase II study of weekly versus every 3 week ixabepilone plus bevacizumab (ixa/bev) versus paclitaxel plus bev (pac/bev) as first-line therapy for metastatic breast cancer (MBC): Final results.

Abstract

1040 Background: Pac/bev is superior to pac alone as first-line therapy for MBC. Ixa/bev has greater preclinical activity than pac/bev in human tumor models. The primary objective of this trial was to evaluate objective response rates (ORR) of ixa/bev given weekly or every 3 weeks relative to pac/bev as first-line therapy for women with advanced breast cancer. Methods: Women with measurable HER2-negative tumors and no prior chemotherapy for advanced breast cancer were randomized in a 3:3:2 ratio to Arm A (ixa 16 mg/m2 IV on days 1, 8, and 15 q28 days/ bev 10 mg/kg IV q 2 wks), Arm B (ixa 40 mg/m2 IV q3 wks /bev 15 mg/kg IV q 3 wks) or Arm C (pac 90 mg/m2 IV, schedule/bev as in Arm A). Treatment was continued until disease progression or unacceptable toxicity. Results: Final efficacy and safety results of all randomized/treated subjects are presented here. Baseline characteristics were balanced between arms except for hormone receptor status, liver metastasis, and time from diagnosis to randomization, which favored arm C. Exposure to chemotherapy in each arm was comparable; median cycles for bev received was 6.0 for Arm A and 10.5 for arms B and C. Conclusions: Ixa/bev given weekly or q 3 wks demonstrated encouraging clinical activity relative to pac/bev, although observed efficacy was better in the q 3 wks arm. Safety profile was manageable and similar to pac/bev in first-line treatment of MBC. These results support ongoing clinical trials of ixa in first-line MBC, and in combination with bev. Ixa (weekly)+ bev Ixa (q3wks) + bev Pac + bev Arm A (N=46)* Arm B (N=45) Arm C (N=32) Baseline characteristics (%) ER+/PR+ 70 58 75 ER+/PR- 9 20 9 Triple-negative 17 20 16 Liver metastasis 48 47 28 Median time from initial diagnosis to randomization (wks) 39 38 55 Efficacy ORR, % (95% CI) 48 (32.9- 63.1) 71 (55.7-83.6) 63 (43.7-78.9) Median PFS (mo) (95% CI) 9.6 (6.1-11.7) 11.9 (8.7-14.7) 13.5 (10.0- 18.2) Safety, % Grade 3 peripheral neuropathy 18 24 25 Grade 3/4 neutropenia 16 60 22 Febrile neutropenia 0 2 0 * N > 45 treated subjects. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb, GlaxoSmithKline, Novartis, Roche, sanofi-aventis Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb, Genentech