title: First-line treatment of advanced breast cancer with sunitinib in combination with docetaxel versus docetaxel alone: results of a prospective, randomized phase III study.
abstract: OBJECTIVE
  To investigate whether sunitinib plus docetaxel improves clinical outcomes for patients with human epidermal growth factor receptor 2 (HER2)/neu-negative advanced breast cancer (ABC) versus docetaxel alone.
  
  
  METHODS
  In this phase III study, patients were randomly assigned to open-label combination therapy (sunitinib 37.5 mg/d, days 2 to 15 every 3 weeks; and docetaxel 75 mg/m(2), day 1 every 3 weeks) or monotherapy (docetaxel 100 mg/m(2) every 3 weeks). Progression-free survival (PFS) was the primary end point.
  
  
  RESULTS
  Two hundred ninety-six patients were randomly assigned to combination therapy, and 297 patients were assigned to monotherapy. Median PFS times were 8.6 and 8.3 months with combination therapy and monotherapy, respectively (hazard ratio, 0.92; one-sided P = .265). The objective response rate (ORR) was significantly higher with the combination (55%) than with monotherapy (42%; one-sided P = .001). Duration of response was similar in both arms (7.5 months with the combination v 7.2 months with monotherapy). Median overall survival (OS) times were 24.8 and 25.5 months with combination therapy and monotherapy, respectively (one-sided P = .904). There were 107 deaths with the combination and 91 deaths with monotherapy. The frequency of common adverse events (AEs) was higher with the combination, as were treatment discontinuations caused by AEs.
  
  
  CONCLUSIONS
  The combination of sunitinib plus docetaxel improved ORR but did not prolong either PFS or OS compared with docetaxel alone when given to an unselected HER2/neu-negative cohort as first-line treatment for ABC. Sunitinib combination therapy may also have resulted in AEs that yield an unfavorable risk-benefit ratio. The sunitinib-docetaxel regimen evaluated in this study is not recommended for further use in ABC.
authors.affiliation: Karolinska Institutet and University Hospital, 171 76 Stockholm, Sweden. jonas.bergh@ki.se
authors.forename: Jonas
authors.initials: J
authors.lastname: Bergh
authors.forename: Igor M
authors.initials: IM
authors.lastname: Bondarenko
authors.forename: Mikhail R
authors.initials: MR
authors.lastname: Lichinitser
authors.forename: Annelie
authors.initials: A
authors.lastname: Liljegren
authors.forename: Richard
authors.initials: R
authors.lastname: Greil
authors.forename: Nataliya L
authors.initials: NL
authors.lastname: Voytko
authors.forename: Anatoly N
authors.initials: AN
authors.lastname: Makhson
authors.forename: Javier
authors.initials: J
authors.lastname: Cortes
authors.forename: Alain
authors.initials: A
authors.lastname: Lortholary
authors.forename: Joachim
authors.initials: J
authors.lastname: Bischoff
authors.forename: Arlene
authors.initials: A
authors.lastname: Chan
authors.forename: Suzette
authors.initials: S
authors.lastname: Delaloge
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Kern
authors.forename: Carla
authors.initials: C
authors.lastname: Giorgetti
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D018275:Carcinoma, Lobular / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D000077143:Docetaxel; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D007390:International Agencies; D008875:Middle Aged; D011446:Prospective Studies; D011758:Pyrroles / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D000077210:Sunitinib; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000077143:Docetaxel; D007211:Indoles; D011758:Pyrroles; D018719:Erb-b2 Receptor Tyrosine Kinases; D000077210:Sunitinib; D043823:Taxoids