title: German adjuvant intergroup node-positive study: a phase III trial to compare oral ibandronate versus observation in patients with high-risk early breast cancer.
abstract: OBJECTIVE
  Bisphosphonates prevent skeletal-related events in patients with metastatic breast cancer. Their effect in early breast cancer is controversial. Ibandronate is an orally and intravenously available amino-bisphosphonate with a favorable toxicity profile. It therefore qualifies as potential agent for adjuvant use.
  
  
  METHODS
  The GAIN (German Adjuvant Intergroup Node-Positive) study was an open-label, randomized, controlled phase III trial with a 2 × 2 factorial design. Patients with node-positive early breast cancer were randomly assigned 1:1 to two different dose-dense chemotherapy regimens and 2:1 to ibandronate 50 mg per day orally for 2 years or observation. In all, 2,640 patients and 728 events were estimated to be required to demonstrate an increase in disease-free survival (DFS) by ibandronate from 75% to 79.5% by using a two-sided α = .05 and 1-β of 80%. We report here the efficacy analysis for ibandronate, which was released by the independent data monitoring committee because the futility boundary was not crossed after 50% of the required DFS events were observed.
  
  
  RESULTS
  Between June 2004 and August 2008, 2,015 patients were randomly assigned to ibandronate and 1,008 to observation. Patients randomly assigned to ibandronate showed no superior DFS or overall survival (OS) compared with patients randomly assigned to observation (DFS: hazard ratio, 0.945; 95% CI, 0.768 to 1.161; P = .589; OS: HR, 1.040; 95% CI, 0.763 to 1.419; P = .803). DFS was numerically longer if ibandronate was used in patients younger than 40 years or older than 60 years compared with patients age 40 to 59 years (test for interaction P = .093).
  
  
  CONCLUSIONS
  Adjuvant treatment with oral ibandronate did not improve outcome of patients with high-risk early breast cancer who received dose-dense chemotherapy.
authors: Gunter von Minckwitz, Valentina Nekljudova, and Sibylle Loibl, German Breast Group, Neu-Isenburg; Volker Möbus, Klinikum Frankfurt-Hoechst, Frankfurt; Andreas Schneeweiss, National Center for Tumor Diseases Heidelberg, Heidelberg; Jens Huober, University Hospital Düsseldorf, Düsseldorf; Christoph Thomssen, University Hospital Halle an der Saale, Halle an der Saale; Michael Untch, Helios Klinikum Berlin Buch, Berlin; Christian Jackisch, Klinikum Offenbach, Offenbach; Ingo J. Diel, Schwerpunktpraxis für gynäkologische Onkologie, Mannheim; Dirk Elling, Sana Klinikum Lichtenberg, Lichtenberg; Bettina Conrad, Frauenklinik, Kassel; Rolf Kreienberg, University Hospital Ulm, Ulm; Volkmar Müller, University Hospital Hamburg, Hamburg; Hans-Joachim Lück, Praxis Hannover; Stefanie Noeding, Nordstadt Krankenhaus, Hannover; Ingo Bauerfeind, Frauenklinik Landshut, Landshut; Michael Clemens, Klinikum Trier, Trier; Marcus Schmidt, University Hospital Mainz, Mainz; Helmut Forstbauer, Haematologic-Oncologic Praxis, Troisdorf; Jana Barinoff, Klinikum Mitte, Essen; Antje Belau, University Hospital, Greifswald; and Nadia Harbeck, Universität München, München, Germany.
authors: Gunter
authors: G
authors: von Minckwitz
authors: Volker
authors: V
authors: Möbus
authors: Andreas
authors: A
authors: Schneeweiss
authors: Jens
authors: J
authors: Huober
authors: Christoph
authors: C
authors: Thomssen
authors: Michael
authors: M
authors: Untch
authors: Christian
authors: C
authors: Jackisch
authors: Ingo J
authors: IJ
authors: Diel
authors: Dirk
authors: D
authors: Elling
authors: Bettina
authors: B
authors: Conrad
authors: Rolf
authors: R
authors: Kreienberg
authors: Volkmar
authors: V
authors: Müller
authors: Hans-Joachim
authors: HJ
authors: Lück
authors: Ingo
authors: I
authors: Bauerfeind
authors: Michael
authors: M
authors: Clemens
authors: Marcus
authors: M
authors: Schmidt
authors: Stefanie
authors: S
authors: Noeding
authors: Helmut
authors: H
authors: Forstbauer
authors: Jana
authors: J
authors: Barinoff
authors: Antje
authors: A
authors: Belau
authors: Valentina
authors: V
authors: Nekljudova
authors: Nadia
authors: N
authors: Harbeck
authors: Sibylle
authors: S
authors: Loibl
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000069287:Capecitabine; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018275:Carcinoma, Lobular / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004164:Diphosphonates / Q000008:administration & dosage; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D005500:Follow-Up Studies; D005858:Germany; D006801:Humans; D000077557:Ibandronic Acid; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D015996:Survival Rate; D055815:Young Adult
chemical_list: D004164:Diphosphonates; D003841:Deoxycytidine; D015251:Epirubicin; D000069287:Capecitabine; D003520:Cyclophosphamide; D017239:Paclitaxel; D005472:Fluorouracil; D000077557:Ibandronic Acid