Nanoparticle albumin-bound paclitaxel (nab-P) and bevacizumab have each demonstrated efficacy in patients with MBC. This trial was designed to further develop nab-P by evaluating its efficacy and safety using every 3 weeks (q3w), every 2 weeks (q2w), or weekly scheduling in combination with bevacizumab as first-line treatment of MBC.
Patients and Methods
This open-label phase II study randomized patients to nab-P 260 mg/m2 q3w (arm A) vs. 260 mg/m2 q2w with filgrastim (arm B) vs. 130 mg/m2 weekly uninterrupted, all with bevacizumab (15 mg/kg q3w arm A, 10 mg/kg q2w arms B and C). The primary endpoints were overall response rate (ORR) and toxicity. Time to tumor progression (TTP) and overall survival were secondary endpoints.
Of 212 patients randomized, 208 (arm A, 75; arm B, 54; arm C, 79) were treated. Arm B was closed early due to toxicity, with more grade ≥ 2 fatigue (arm A, 46%; arm B, 62%; arm C, 62%) and bone pain (arm A, 11%; arm B, 23%; arm C, 5%). Neurotoxicity grade ≥ 2 was equivalent across the arms (> 50%) and reversible for most patients. Febrile neutropenia occurred in ≤ 3% of patients in all arms. ORR was similar among the arms (arm A, 45%; arm B, 41%; arm C, 46%). Median TTP was slightly longer in arm C (9.0 months) vs. arms A (8.0 months) and B (5.8 months) (overall, P = .105).
Significant antitumor activity was observed in all the arms. Weekly nab-P with bevacizumab appeared to have the highest therapeutic index. However, sensory neuropathy was treatment limiting, which suggests that a 3 weeks on and 1 week off schedule should be explored.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Clinical Breast Cancer
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer.J Clin Oncol. 2005; 23: 7794-7803
- Phase I and pharmacokinetic study of ABI-007, a Cremophor-free, protein-stabilized, nanoparticle formulation of paclitaxel.Clin Cancer Res. 2002; 8: 1038-1044
- Phase I and pharmacokinetics trial of ABI-007, a novel nanoparticle formulation of paclitaxel in patients with advanced nonhematologic malignancies.J Clin Oncol. 2005; 23: 7785-7793
- Significantly longer progression-free survival with nab-paclitaxel compared with docetaxel as first-line therapy for metastatic breast cancer.J Clin Oncol. 2009; 27: 3611-3619
- Phase II study of weekly albumin-bound paclitaxel for patients with metastatic breast cancer heavily pretreated with taxanes.Clin Breast Cancer. 2007; 7: 850-856
- Phase II trial of nab-paclitaxel compared with docetaxel as first-line chemotherapy in patients with metastatic breast cancer: final analysis of overall survival.Clin Breast Cancer. 2012; 12: 313-321
- Avastin® (bevacizumab) [prescibing information]. Genentech, South San Francisco, CA2012
- Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer.J Clin Oncol. 2005; 23: 792-799
- Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer.N Engl J Med. 2007; 357: 2666-2676
- Phase III study of bevacizumab plus docetaxel compared with placebo plus docetaxel for the first-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer.J Clin Oncol. 2010; 28: 3239-3247
- Ribbon-1: Randomized, double blind, placebo-controlled, phase II trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor-2 negative, locally recurrent or metastatic breast cancer.J Clin Oncol. 2011; 29: 1252-1260
- RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer.J Clin Oncol. 2011; 29: 4286-4293
- Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup trial C9741/Cancer and Leukemia Group B trial 9741.J Clin Oncol. 2003; 21: 1431-1439
- Adjuvant dose-dense doxorubicin plus cyclophosphamide followed by dose-dense nab-paclitaxel is safe in women with early-stage breast cancer: a pilot study.Breast Cancer Res Treat. 2011; 125: 115-120
- A feasibility study of bevacizumab plus dose-dense doxorubicin-cyclophosphamide (AC) followed by nanoparticle albumin-bound paclitaxel in early-stage breast cancer.Clin Cancer Res. 2011; 17: 3398-3407
- Synergy of nab-paclitaxel and bevacizumab in eradicating large orthotopic breast tumors and preexisting metastases.Neoplasia. 2011; 13: 327-338
- New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada.J Natl Cancer Inst. 2000; 92: 205-216
- Randomized phase III trial of weekly compared with every-3-weeks paclitaxel for metastatic breast cancer, with trastuzumab for all HER-2 overexpressors and random assignment to trastuzumab or not in HER-2 nonoverexpressors: final results of Cancer and Leukemia Group B protocol 9840.J Clin Oncol. 2008; 26: 1642-1649
- Anglo-Celtic IV: first results of a UK National Cancer Research Network randomized phase III pharmacogenetic trial of weekly compared to 3 weekly paclitaxel in patients with locally advanced or metastatic breast cancer (ABC).J Clin Oncol. 2007; 25 (abstract LBA1005)
- Prognostic factors predicting survival from first recurrence in patients with metastatic breast cancer: analysis of 439 patients.Breast Cancer Res Treat. 1999; 56: 67-78
- Human breast cancer: survival from first metastasis. Breast Cancer Study Group.Breast Cancer Res Treat. 1992; 21: 173-180
- The significance of the site of recurrence to subsequent breast cancer survival.Eur J Surg Oncol. 2007; 33: 420-423
- Phase II trial of weekly nab-paclitaxel in combination with bevacizumab as first-line treatment in metastatic breast cancer.J Clin Oncol. 2008; 26 (1075 (abstract))
- A phase II study of weekly nanoparticle albumin-bound paclitaxel with or without trastuzumab in metastatic breast cancer.Clin Breast Cancer. 2011; 11: 121-128
- Phase II trial of weekly nab (nanoparticle albumin-bound)-paclitaxel (nab-paclitaxel) (Abraxane) in combination with gemcitabine in patients with metastatic breast cancer (N0531).Ann Oncol. 2009; 20: 449-453
- Phase II multicenter trial of albumin-bound paclitaxel and capecitabine in first-line treatment of patients with metastatic breast cancer.Clin Breast Cancer. 2012; 12: 87-93
- CALGB 40502/NCCTG N063H: randomized phase III trial of weekly paclitaxel (P) compared to weekly nanoparticle albumin bound nab-paclitaxel (NP) or ixabepilone (ix) with or without bevacizumab (B) as first-line therapy for locally recurrent or metastatic breast cancer (MBC).J Clin Oncol. 2012; 30 (abstract).: 1002
Accepted: February 26, 2013
Received: November 27, 2012
© 2013 Elsevier Inc. Published by Elsevier Inc. All rights reserved.