A feasibility study of bevacizumab plus dose-dense doxorubicin- cyclophosphamide (AC) followed by nanoparticle albumin-bound paclitaxel in early-stage breast cancer

Heather L. McArthur, Hope Rugo, Benjamin Nulsen, Laura Hawks, Jill Grothusen, Michelle Melisko, Mark Moasser, Matthew Paulson, Tiffany Traina, Sujata Patil, Qin Zhou, Richard Steingart, Chau Dang, Monica Morrow, Peter Cordeiro, Monica Fornier, John Park, Andrew Seidman, Diana Lake, Theresa GilewskiMaria Theodoulou, Shanu Modi, Gabriella D'Andrea, Nancy Sklarin, Mark Robson, Mary Ellen Moynahan, Steven Sugarman, Jane E. Sealey, John H. Laragh, Carmen Merali, Larry Norton, Clifford A. Hudis, Maura N. Dickler

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Purpose: Bevacizumab confers benefits in metastatic breast cancer but may be more effective as adjuvant therapy. We evaluated the cardiac safety of bevacizumab plus dose-dense doxorubicin-cyclophosphamide (ddAC) → nanoparticle albumin-bound (nab)-paclitaxel in human epidermal growth factor receptor 2 normal early-stage breast cancer. Experimental Design: Eighty patients with normal left ventricular ejection fraction (LVEF) were enrolled. Bevacizumab was administered for 1 year, concurrently with ddAC → nab-paclitaxel then as a single agent. LVEF was evaluated at months 0, 2, 6, 9, and 18. This regimen was considered safe if fewer than three cardiac events or fewer than two deaths from left ventricular dysfunction occurred. Correlative studies of cardiac troponin (cTn) and plasma renin activity (PRA) were conducted. Results: The median age was 48 years (range, 27-75 years), and baseline LVEF was 68% (53%-82%). After 39 months' median follow-up (5-45 months): median LVEF was 68% (53%-80%) at 2 months (n = 78), 64% (51%-77%) at 6 months (n=66), 63% (48%-77%) at 9 months (n=61), and 66% (42%-76%) at 18 months (n = 54). One patient developed symptomatic LV dysfunction at month 15. Common toxicities necessitating treatment discontinuation were hypertension (HTN, 4%), wound-healing complications (4%), and asymptomatic LVEF declines (4%). Neither cTn nor PRA predicted congestive heart failure (CHF) or HTN, respectively. Conclusions: Bevacizumab with ddAC → nab-paclitaxel had a low rate of cardiac events; cTn and PRA levels are not predictive of CHF or HTN, respectively. The efficacy of bevacizumab as adjuvant treatment will be established in several ongoing phase III trials.

Original languageEnglish (US)
Pages (from-to)3398-3407
Number of pages10
JournalClinical Cancer Research
Volume17
Issue number10
DOIs
StatePublished - May 15 2011
Externally publishedYes

ASJC Scopus subject areas

  • General Medicine

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