title: Randomized phase II trial of weekly vs. every 2 weeks vs. every 3 weeks nanoparticle albumin-bound paclitaxel with bevacizumab as first-line chemotherapy for metastatic breast cancer.
abstract: BACKGROUND
  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.
  
  
  METHODS
  This open-label phase II study randomized patients to nab-P 260 mg/m(2) q3w (arm A) vs. 260 mg/m(2) q2w with filgrastim (arm B) vs. 130 mg/m(2) 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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Memorial Sloan-Kettering Cancer Center, Department of Medicine, Division of Solid Tumor Oncology, New York, NY 10065, USA. seidmana@mskcc.org
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Seidman
authors.forename: Alison K
authors.initials: AK
authors.lastname: Conlin
authors.forename: Ariadne
authors.initials: A
authors.lastname: Bach
authors.forename: Mary Ellen
authors.initials: ME
authors.lastname: Moynahan
authors.forename: Diana
authors.initials: D
authors.lastname: Lake
authors.forename: Andres
authors.initials: A
authors.lastname: Forero
authors.forename: Gail Shaw
authors.initials: GS
authors.lastname: Wright
authors.forename: Mary Helen
authors.initials: MH
authors.lastname: Hackney
authors.forename: Alicia
authors.initials: A
authors.lastname: Clawson
authors.forename: Larry
authors.initials: L
authors.lastname: Norton
authors.forename: Clifford A
authors.initials: CA
authors.lastname: Hudis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000068196:Albumin-Bound Paclitaxel; D000418:Albumins / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D015996:Survival Rate
chemical_list: D000068196:Albumin-Bound Paclitaxel; D000418:Albumins; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D017239:Paclitaxel
keywords: Combination therapy; Human epidermal growth factor receptor 2 negative; Nanoparticle albumin-bound paclitaxel; Neuropathy; Taxanes