PMID- 24674873
OWN - NLM
STAT- MEDLINE
DCOM- 20150112
LR  - 20211021
IS  - 1549-490X (Electronic)
IS  - 1083-7159 (Print)
IS  - 1083-7159 (Linking)
VI  - 19
IP  - 4
DP  - 2014 Apr
TI  - Bosutinib in combination with the aromatase inhibitor exemestane: a phase II 
      trial in postmenopausal women with previously treated locally advanced or 
      metastatic hormone receptor-positive/HER2-negative breast cancer.
PG  - 346-7
LID - 10.1634/theoncologist.2014-0022 [doi]
AB  - BACKGROUND: Bosutinib is an oral, selective Src/Abl tyrosine kinase inhibitor 
      with activity in breast cancer (BC). We evaluated bosutinib plus exemestane as 
      second-line therapy in previously treated hormone receptor-positive (HR+) locally 
      advanced or metastatic BC. METHODS: This was a phase II study with patients 
      enrolled in a single-arm safety lead-in phase. Patients receiving bosutinib at 
      400 mg or 300 mg/day (based on toxicity) plus exemestane at 25 mg/day were 
      monitored for adverse events (AEs) and dose-limiting toxicities for 28 days, and 
      initial efficacy was assessed. After the lead-in and dose-determination phase, 
      randomized evaluation of combination therapy versus exemestane was planned. 
      RESULTS: Thirty-nine of 42 patients (93%) experienced treatment-related AEs 
      including diarrhea in 28 (67%) and hepatotoxicity in 11 (26%); overall serious 
      treatment-related AEs were recorded in 4 (10%). No liver toxicity met Hy's law 
      criteria. Dose-limiting toxicities occurred in 5 of 13 patients receiving 400 mg 
      (38%) and 3 of 26 patients receiving 300 mg (12%) of bosutinib; all resolved on 
      treatment discontinuation. One patient (300 mg/day) achieved confirmed partial 
      response; three (400 mg/day, n = 2; 300 mg/day, n = 1) maintained stable disease 
      for >24 weeks; a best response of progressive disease occurred in 15 of 42 
      patients (36%). Median progression-free survival was 12.3 weeks (80% confidence 
      interval: 11.0-15.6). CONCLUSION: The risk-benefit profile of bosutinib at 300 
      mg/day plus exemestane resulted in early study termination before the randomized 
      portion. Alternative bosutinib regimens merit investigation in BC.
FAU - Moy, Beverly
AU  - Moy B
AD  - Massachusetts General Hospital, Boston, Massachusetts, USA;
FAU - Neven, Patrick
AU  - Neven P
FAU - Lebrun, Fabienne
AU  - Lebrun F
FAU - Bellet, Meritxell
AU  - Bellet M
FAU - Xu, Binghe
AU  - Xu B
FAU - Sarosiek, Tomasz
AU  - Sarosiek T
FAU - Chow, Louis
AU  - Chow L
FAU - Goss, Paul
AU  - Goss P
FAU - Zacharchuk, Charles
AU  - Zacharchuk C
FAU - Leip, Eric
AU  - Leip E
FAU - Turnbull, Kathleen
AU  - Turnbull K
FAU - Bardy-Bouxin, Nathalie
AU  - Bardy-Bouxin N
FAU - Duvillie, Ladan
AU  - Duvillie L
FAU - Lang, Istvan
AU  - Lang I
LA  - eng
SI  - ClinicalTrials.gov/NCT00793546
PT  - Clinical Trial, Phase II
PT  - Journal Article
DEP - 20140327
PL  - England
TA  - Oncologist
JT  - The oncologist
JID - 9607837
RN  - 0 (Androstadienes)
RN  - 0 (Aniline Compounds)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Aromatase Inhibitors)
RN  - 0 (Nitriles)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Quinolines)
RN  - 0 (Receptors, Estrogen)
RN  - 0 (Receptors, Progesterone)
RN  - 5018V4AEZ0 (bosutinib)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - NY22HMQ4BX (exemestane)
SB  - IM
MH  - Androstadienes/adverse effects/*therapeutic use
MH  - Aniline Compounds/adverse effects/*therapeutic use
MH  - Antineoplastic Agents/adverse effects/therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use
MH  - Aromatase Inhibitors/adverse effects/*therapeutic use
MH  - Breast Neoplasms/*drug therapy
MH  - Disease-Free Survival
MH  - Female
MH  - Humans
MH  - Nitriles/adverse effects/*therapeutic use
MH  - Postmenopause
MH  - Protein Kinase Inhibitors/adverse effects/therapeutic use
MH  - Quinolines/adverse effects/*therapeutic use
MH  - Receptor, ErbB-2/metabolism
MH  - Receptors, Estrogen/metabolism
MH  - Receptors, Progesterone/metabolism
PMC - PMC3983831
EDAT- 2014/03/29 06:00
MHDA- 2015/01/13 06:00
PMCR- 2014/03/27
CRDT- 2014/03/29 06:00
PHST- 2014/03/29 06:00 [entrez]
PHST- 2014/03/29 06:00 [pubmed]
PHST- 2015/01/13 06:00 [medline]
PHST- 2014/03/27 00:00 [pmc-release]
AID - theoncologist.2014-0022 [pii]
AID - T1422 [pii]
AID - 10.1634/theoncologist.2014-0022 [doi]
PST - ppublish
SO  - Oncologist. 2014 Apr;19(4):346-7. doi: 10.1634/theoncologist.2014-0022. Epub 2014 
      Mar 27.