title: Trastuzumab beyond progression in human epidermal growth factor receptor 2-positive advanced breast cancer: a german breast group 26/breast international group 03-05 study.
abstract: OBJECTIVE
  Trastuzumab shows clinical activity in human epidermal growth factor receptor 2 (HER-2)-positive early and advanced breast cancer. In the German Breast Group 26/Breast International Group 03-05 trial, we investigated if trastuzumab treatment should be continued beyond progression.
  
  
  METHODS
  Patients with HER-2-positive breast cancer that progresses during treatment with trastuzumab were randomly assigned to receive capecitabine (2,500 mg/m(2) body-surface area on days 1 through 14 [1,250 mg/m(2) semi-daily]) alone or with continuation of trastuzumab (6 mg/kg body weight) in 3-week cycles. The primary end point was time to progression.
  
  
  RESULTS
  We randomly assigned 78 patients to capecitabine and 78 patients to capecitabine plus trastuzumab. Sixty-five events and 38 deaths in the capecitabine group and 62 events and 33 deaths in the capecitabine-plus-trastuzumab group occurred during 15.6 months of follow-up. Median times to progression were 5.6 months in the capecitabine group and 8.2 months in the capecitabine-plus-trastuzumab group with an unadjusted hazard ratio of 0.69 (95% CI, 0.48 to 0.97; two-sided log-rank P = .0338). Overall survival rates were 20.4 months (95% CI, 17.8 to 24.7) in the capecitabine group and 25.5 months (95% CI, 19.0 to 30.7) in the capecitabine-plus-trastuzumab group (P = .257). Overall response rates were 27.0% with capecitabine and 48.1% with capecitabine plus trastuzumab (odds ratio, 2.50; P = .0115). Continuation of trastuzumab beyond progression was not associated with increased toxicity.
  
  
  CONCLUSIONS
  Continuation of trastuzumab plus capecitabine showed a significant improvement in overall response and time to progression compared with capecitabine alone in women with HER-2-positive breast cancer who experienced progression during trastuzumab treatment.
authors.affiliation: GBG Forschungs GmbH, University of Frankfurt, Schleussnerstr 42, Neu-Isenburg, Germany 63263. Gunter.vonMinckwitz@germanbreastgroup.de
authors.forename: Gunter
authors.initials: G
authors.lastname: von Minckwitz
authors.forename: Andreas
authors.initials: A
authors.lastname: du Bois
authors.forename: Marcus
authors.initials: M
authors.lastname: Schmidt
authors.forename: Nicolai
authors.initials: N
authors.lastname: Maass
authors.forename: Tanja
authors.initials: T
authors.lastname: Cufer
authors.forename: Felix E
authors.initials: FE
authors.lastname: de Jongh
authors.forename: Eduard
authors.initials: E
authors.lastname: Maartense
authors.forename: Christoph
authors.initials: C
authors.lastname: Zielinski
authors.forename: Manfred
authors.initials: M
authors.lastname: Kaufmann
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Bauer
authors.forename: Klaus H
authors.initials: KH
authors.lastname: Baumann
authors.forename: Michael R
authors.initials: MR
authors.lastname: Clemens
authors.forename: Ralph
authors.initials: R
authors.lastname: Duerr
authors.forename: Christoph
authors.initials: C
authors.lastname: Uleer
authors.forename: Michael
authors.initials: M
authors.lastname: Andersson
authors.forename: Robert C
authors.initials: RC
authors.lastname: Stein
authors.forename: Valentina
authors.initials: V
authors.lastname: Nekljudova
authors.forename: Sibylle
authors.initials: S
authors.lastname: Loibl
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D000069287:Capecitabine; D017024:Chemotherapy, Adjuvant; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D007390:International Agencies; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D012307:Risk Factors; D015996:Survival Rate; D013997:Time Factors; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000069287:Capecitabine; D003841:Deoxycytidine; D005472:Fluorouracil; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab