title: Phase III trial of sunitinib in combination with capecitabine versus capecitabine monotherapy for the treatment of patients with pretreated metastatic breast cancer.
abstract: OBJECTIVE
  Metastatic breast cancer (MBC) remains an incurable illness in the majority of cases, despite major therapeutic advances. This may be related to the ability of breast tumors to induce neoangiogenesis, even in the face of cytotoxic chemotherapy. Sunitinib, an inhibitor of key molecules involved in neoangiogenesis, has an established role in the treatment of metastatic renal cell and other cancers and demonstrated activity in a phase II trial in MBC. We performed a randomized phase III trial comparing sunitinib plus capecitabine (2,000 mg/m2) with single-agent capecitabine (2,500 mg/m2) in patients with heavily pretreated MBC.
  
  
  METHODS
  Eligibility criteria included MBC, prior therapy with anthracyclines and taxanes, one or two prior chemotherapy regimens for metastatic disease or early relapse after a taxane plus anthracycline adjuvant regimen, and adequate organ function and performance status. The primary end point was progression-free survival, for which the study had 90% power to detect a 50% improvement (from 4 to 6 months).
  
  
  RESULTS
  A total of 442 patients were randomly assigned. Progression-free survival was not significantly different between the treatment arms, with medians of 5.5 months (95% CI, 4.5 to 6.0) for the sunitinib plus capecitabine arm and 5.9 months (95% CI, 5.4 to 7.6) for the capecitabine monotherapy arm (hazard ratio, 1.22; 95% CI, 0.95 to 1.58; one-sided P = .941). There were no significant differences in response rate or overall survival. Toxicity, except for hand-foot syndrome, was more severe in the combination arm.
  
  
  CONCLUSIONS
  The addition of sunitinib to capecitabine does not improve the clinical outcome of patients with MBC pretreated with anthracyclines and taxanes.
authors.affiliation: Irish Cooperative Oncology Research Group, Dublin, Ireland.
authors.forename: John P
authors.initials: JP
authors.lastname: Crown
authors.forename: Véronique
authors.initials: V
authors.lastname: Diéras
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Staroslawska
authors.forename: Denise A
authors.initials: DA
authors.lastname: Yardley
authors.forename: Thomas
authors.initials: T
authors.lastname: Bachelot
authors.forename: Neville
authors.initials: N
authors.lastname: Davidson
authors.forename: Hans
authors.initials: H
authors.lastname: Wildiers
authors.forename: Peter A
authors.initials: PA
authors.lastname: Fasching
authors.forename: Olivier
authors.initials: O
authors.lastname: Capitain
authors.forename: Manuel
authors.initials: M
authors.lastname: Ramos
authors.forename: Richard
authors.initials: R
authors.lastname: Greil
authors.forename: Francesco
authors.initials: F
authors.lastname: Cognetti
authors.forename: George
authors.initials: G
authors.lastname: Fountzilas
authors.forename: Maria
authors.initials: M
authors.lastname: Blasinska-Morawiec
authors.forename: Cornelia
authors.initials: C
authors.lastname: Liedtke
authors.forename: Rolf
authors.initials: R
authors.lastname: Kreienberg
authors.forename: Wilson H
authors.initials: WH
authors.lastname: Miller
authors.forename: Vanessa
authors.initials: V
authors.lastname: Tassell
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.forename: Jolanda
authors.initials: J
authors.lastname: Paolini
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Kern
authors.forename: Gilles
authors.initials: G
authors.lastname: Romieu
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011446:Prospective Studies; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects; D000077210:Sunitinib; D055815:Young Adult
chemical_list: D007211:Indoles; D011758:Pyrroles; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil; D000077210:Sunitinib