PMID- 22763464
OWN - NLM
STAT- MEDLINE
DCOM- 20121213
LR  - 20211021
IS  - 1573-7217 (Electronic)
IS  - 0167-6806 (Print)
IS  - 0167-6806 (Linking)
VI  - 134
IP  - 3
DP  - 2012 Aug
TI  - A phase II trial to assess efficacy and safety of afatinib in extensively 
      pretreated patients with HER2-negative metastatic breast cancer.
PG  - 1149-59
LID - 10.1007/s10549-012-2126-1 [doi]
AB  - Afatinib (BIBW 2992) is an ErbB-family blocker that irreversibly inhibits 
      signaling from all relevant ErbB-family dimers. Afatinib has demonstrated 
      preclinical activity in human epidermal growth factor receptor HER2 
      (ErbB2)-positive and triple-negative xenograft models of breast cancer, and 
      clinical activity in phase I studies. This was a multicenter phase II study 
      enrolling patients with HER2-negative metastatic breast cancer progressing 
      following no more than three lines of chemotherapy. No prior epidermal growth 
      factor receptor-targeted therapy was allowed. Patients received 50-mg afatinib 
      once daily until disease progression. Tumor assessment was performed at every 
      other 28-day treatment course. The primary endpoint was clinical benefit (CB) for 
      >/=4 treatment courses in triple-negative (Cohort A) metastatic breast cancer 
      (TNBC) and objective responses measured by Response Evaluation Criteria in Solid 
      Tumors in patients with HER2-negative, estrogen receptor-positive, and/or 
      progesterone receptor-positive breast cancer (Cohort B). Fifty patients received 
      treatment, including 29 patients in Cohort A and 21 patients in Cohort B. No 
      objective responses were observed in either cohort. Median progression-free 
      survival was 7.4 and 7.7 weeks in Cohorts A and B, respectively. Three patients 
      with TNBC had stable disease for >/=4 treatment courses, one of them for 12 courses 
      (median 26.3 weeks; range 18.9-47.9 weeks). The most frequently observed 
      afatinib-associated adverse events (AEs) were gastrointestinal and skin-related 
      side effects, which were manageable by symptomatic treatment and dose reductions. 
      Afatinib pharmacokinetics were comparable to those observed in previously 
      reported phase I trials. In conclusion, afatinib had limited activity in 
      HER2-negative breast cancer. AEs were generally manageable and mainly affected 
      the skin and the gastrointestinal tract.
FAU - Schuler, Martin
AU  - Schuler M
AD  - Department of Medical Oncology, West German Cancer Center, University Hospital 
      Essen, University of Duisburg-Essen, Essen, Germany.
FAU - Awada, Ahmad
AU  - Awada A
FAU - Harter, Philipp
AU  - Harter P
FAU - Canon, Jean Luc
AU  - Canon JL
FAU - Possinger, Kurt
AU  - Possinger K
FAU - Schmidt, Marcus
AU  - Schmidt M
FAU - De Greve, Jacques
AU  - De Greve J
FAU - Neven, Patrick
AU  - Neven P
FAU - Dirix, Luc
AU  - Dirix L
FAU - Jonat, Walter
AU  - Jonat W
FAU - Beckmann, Matthias W
AU  - Beckmann MW
FAU - Schutte, Jochen
AU  - Schutte J
FAU - Fasching, Peter A
AU  - Fasching PA
FAU - Gottschalk, Nina
AU  - Gottschalk N
FAU - Besse-Hammer, Tatiana
AU  - Besse-Hammer T
FAU - Fleischer, Frank
AU  - Fleischer F
FAU - Wind, Sven
AU  - Wind S
FAU - Uttenreuther-Fischer, Martina
AU  - Uttenreuther-Fischer M
FAU - Piccart, Martine
AU  - Piccart M
FAU - Harbeck, Nadia
AU  - Harbeck N
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20120705
PL  - Netherlands
TA  - Breast Cancer Res Treat
JT  - Breast cancer research and treatment
JID - 8111104
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Quinazolines)
RN  - 41UD74L59M (Afatinib)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Adult
MH  - Afatinib
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Agents/adverse effects/pharmacology/*therapeutic use
MH  - Biomarkers, Tumor/metabolism
MH  - Breast Neoplasms/*drug therapy/metabolism/mortality/pathology
MH  - Cohort Studies
MH  - Female
MH  - Humans
MH  - Middle Aged
MH  - Neoplasm Metastasis
MH  - Protein Kinase Inhibitors/adverse effects/pharmacology/*therapeutic use
MH  - Quinazolines/administration & dosage/adverse effects/*therapeutic use
MH  - Receptor, ErbB-2/*deficiency/metabolism
MH  - Survival Analysis
MH  - Treatment Outcome
PMC - PMC3409367
EDAT- 2012/07/06 06:00
MHDA- 2012/12/14 06:00
PMCR- 2012/07/05
CRDT- 2012/07/06 06:00
PHST- 2012/05/25 00:00 [received]
PHST- 2012/05/28 00:00 [accepted]
PHST- 2012/07/06 06:00 [entrez]
PHST- 2012/07/06 06:00 [pubmed]
PHST- 2012/12/14 06:00 [medline]
PHST- 2012/07/05 00:00 [pmc-release]
AID - 2126 [pii]
AID - 10.1007/s10549-012-2126-1 [doi]
PST - ppublish
SO  - Breast Cancer Res Treat. 2012 Aug;134(3):1149-59. doi: 10.1007/s10549-012-2126-1. 
      Epub 2012 Jul 5.