title: Sunitinib plus paclitaxel versus bevacizumab plus paclitaxel for first-line treatment of patients with advanced breast cancer: a phase III, randomized, open-label trial.
abstract: BACKGROUND
  A multicenter, open-label phase III study was conducted to test whether sunitinib plus paclitaxel prolongs progression-free survival (PFS) compared with bevacizumab plus paclitaxel as first-line treatment for patients with HER2(-) advanced breast cancer.
  
  
  METHODS
  Patients with HER2(-) advanced breast cancer who were disease free for ≥ 12 months after adjuvant taxane treatment were randomized (1:1; planned enrollment 740 patients) to receive intravenous (I.V.) paclitaxel 90 mg/m(2) every week for 3 weeks in 4-week cycles plus either sunitinib 25 to 37.5 mg every day or bevacizumab 10 mg/kg I.V. every 2 weeks. [corrected]
  
  
  RESULTS
  The trial was terminated early because of futility in reaching the primary endpoint as determined by the independent data monitoring committee during an interim futility analysis. At data cutoff, 242 patients had been randomized to sunitinib-paclitaxel and 243 patients to bevacizumab-paclitaxel. Median PFS was shorter with sunitinib-paclitaxel (7.4 vs. 9.2 months; hazard ratio [HR] 1.63 [95% confidence interval (CI), 1.18-2.25]; 1-sided P = .999). At a median follow-up of 8.1 months, with 79% of sunitinib-paclitaxel and 87% of bevacizumab-paclitaxel patients alive, overall survival analysis favored bevacizumab-paclitaxel (HR 1.82 [95% CI, 1.16-2.86]; 1-sided P = .996). The objective response rate was 32% in both arms, but median duration of response was shorter with sunitinib-paclitaxel (6.3 vs. 14.8 months). Bevacizumab-paclitaxel was better tolerated than sunitinib-paclitaxel. This was primarily due to a high frequency of grade 3/4, treatment-related neutropenia with sunitinib-paclitaxel (52%) precluding delivery of the prescribed doses of both drugs.
  
  
  CONCLUSIONS
  The sunitinib-paclitaxel regimen evaluated in this study was clinically inferior to the bevacizumab-paclitaxel regimen and is not a recommended treatment option for patients with advanced breast cancer.
authors.affiliation: Virginia Cancer Specialists, US Oncology, Fairfax, VA, USA. Nicholas.Robert@USONCOLOGY.COM
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Robert
authors.forename: Mansoor N
authors.initials: MN
authors.lastname: Saleh
authors.forename: Devchand
authors.initials: D
authors.lastname: Paul
authors.forename: Daniele
authors.initials: D
authors.lastname: Generali
authors.forename: Laurent
authors.initials: L
authors.lastname: Gressot
authors.forename: Mehmet S
authors.initials: MS
authors.lastname: Copur
authors.forename: Adam M
authors.initials: AM
authors.lastname: Brufsky
authors.forename: Susan E
authors.initials: SE
authors.lastname: Minton
authors.forename: Jeffrey K
authors.initials: JK
authors.lastname: Giguere
authors.forename: John W
authors.initials: JW
authors.lastname: Smith
authors.forename: Paul D
authors.initials: PD
authors.lastname: Richards
authors.forename: Diana
authors.initials: D
authors.lastname: Gernhardt
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.forename: Katherine F
authors.initials: KF
authors.lastname: Liau
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Kern
authors.forename: John
authors.initials: J
authors.lastname: Davis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002277:Carcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects; D000077210:Sunitinib; D016019:Survival Analysis
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007211:Indoles; D011758:Pyrroles; D000068258:Bevacizumab; D017239:Paclitaxel; D000077210:Sunitinib