title: Trastuzumab beyond progression: overall survival analysis of the GBG 26/BIG 3-05 phase III study in HER2-positive breast cancer.
abstract: BACKGROUND
  Continuation of trastuzumab plus capecitabine (XH) showed a significantly improved overall response rate and time to progression compared with capecitabine (X) alone in women with HER2-positive breast cancer progressing during trastuzumab treatment. Here, we report the final analysis on overall survival.
  
  
  METHODS
  Patients with HER2-positive, advanced breast cancer who progressed during treatment with trastuzumab with or without 1st-line metastatic chemotherapy were prospectively randomised to X (2500mg/m(2) on days 1-14, q3w) or XH (6 (8)mg/kg, q3w). Overall survival was a pre-specified secondary end-point.
  
  
  RESULTS
  Median follow-up at June 2010 was 20.7months. Fifty nine of 74 and 60 of 77 patients died in the X and XH arm, respectively. Median overall survival was 20.6 and 24.9months with X and XH, respectively (HR=0.94 [0.65-1.35]; p=0.73). Performance status and metastatic site were independent prognosticators for overall survival. No difference between treatment arms was observed for patients who achieved clinical response or clinical benefit, respectively. Patients who continued/restarted anti-HER2 treatment (trastuzumab or lapatinib) after 2nd progression (N=52) had a post-progression survival of 18.8 compared with 13.3months for those who did not receive 3rd line treatment with anti-HER2 agents (N=88) (HR 0.63; p=0.02).
  
  
  CONCLUSIONS
  Final overall survival analysis of the GBG-26 study did not demonstrate a significant survival benefit for treatment beyond progression with trastuzumab. However, in a post-hoc analysis, patients receiving anti-HER2 treatment as 3rd line therapy showed a better post-progression survival than those not receiving this targeted treatment.
authors: German Breast Group, GBG ForschungsGmbH, Martin-Behaim Str. 12, 63263 Neu-Isenburg, Germany. Gunter.vonMinckwitz@germanbreastgroup.de
authors: Gunter
authors: G
authors: von Minckwitz
authors: Kathrin
authors: K
authors: Schwedler
authors: Marcus
authors: M
authors: Schmidt
authors: Jana
authors: J
authors: Barinoff
authors: Christoph
authors: C
authors: Mundhenke
authors: Tanja
authors: T
authors: Cufer
authors: Eduard
authors: E
authors: Maartense
authors: Felix E
authors: FE
authors: de Jongh
authors: Klaus H
authors: KH
authors: Baumann
authors: Joachim
authors: J
authors: Bischoff
authors: Nadia
authors: N
authors: Harbeck
authors: Hans-Joachim
authors: HJ
authors: Lück
authors: Nicolai
authors: N
authors: Maass
authors: Christoph
authors: C
authors: Zielinski
authors: Michael
authors: M
authors: Andersson
authors: Robert C
authors: RC
authors: Stein
authors: Valentina
authors: V
authors: Nekljudova
authors: Sibylle
authors: S
authors: Loibl
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality* / Q000473:pathology; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005060:Europe; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D053208:Kaplan-Meier Estimate; D058990:Molecular Targeted Therapy; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018570:Risk Assessment; D012307:Risk Factors; D015996:Survival Rate; D013997:Time Factors; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000069287:Capecitabine; D003841:Deoxycytidine; D005472:Fluorouracil; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human