PMID- 22198412
OWN - NLM
STAT- MEDLINE
DCOM- 20121119
LR  - 20231104
IS  - 1573-7217 (Electronic)
IS  - 0167-6806 (Print)
IS  - 0167-6806 (Linking)
VI  - 134
IP  - 1
DP  - 2012 Jul
TI  - A phase II study of lapatinib and bevacizumab as treatment for 
      HER2-overexpressing metastatic breast cancer.
PG  - 13-20
LID - 10.1007/s10549-011-1918-z [doi]
AB  - Preclinical data have demonstrated that the combination of antihuman epidermal 
      growth factor receptor-2 (anti-HER2) and antivascular endothelial growth factor 
      (anti-VEGF)--targeted agents has antitumor activity; these data indicate certain 
      patients with HER2-overexpressing breast cancer may derive clinical benefit from 
      this combination. The purpose of this single-arm phase II study was to determine 
      the efficacy and safety of the dual-targeting combination of lapatinib and 
      bevacizumab. Women with HER2-overexpressing advanced breast cancer received 1,500 
      mg oral lapatinib daily plus 10 mg/kg IV bevacizumab every 2 weeks. The primary 
      endpoint was progression-free survival (PFS) at week 12; secondary endpoints 
      included overall tumor response rate (ORR), clinical benefit rate (CBR), duration 
      of response, time-to-response, PFS, and safety. Circulating tumor cells (CTC) and 
      circulating endothelial cells (CEC) were measured at baseline and during study 
      treatment as potential response markers. Fifty-two patients with stage IV disease 
      were enrolled. The 12-week investigator-assessed PFS rate was 69.2% (95% 
      confidence interval [CI]: 54.9, 81.3). Median PFS was 24.7 weeks (95% CI: 20.4, 
      35.1), and the CBR was 30.8% (95% CI: 18.7, 45.1). Of 45 patients with measurable 
      disease, 6 were determined to have a partial response per Response Evaluation 
      Criteria in Solid Tumors (ORR: 13.3%; 95% CI: 5.1, 26.8). The most common adverse 
      events (AEs) included diarrhea, rash, and fatigue; most of these were either 
      grade 1 or 2. Clinical responses were correlated with decreases in CTC and CEC. 
      Lapatinib plus bevacizumab was active in patients with HER2-overexpressing breast 
      cancer. The AE profile of the combination was consistent with the known profiles 
      for these agents.
FAU - Rugo, Hope S
AU  - Rugo HS
AD  - Helen Diller Family Comprehensive Cancer Center, University of California San 
      Francisco, 1600 Divisadero St., 2nd Floor, Box 1710, B-608, San Francisco, CA 
      94143, USA. hrugo@medicine.ucsf.edu
FAU - Chien, A Jo
AU  - Chien AJ
FAU - Franco, Sandra X
AU  - Franco SX
FAU - Stopeck, Alison T
AU  - Stopeck AT
FAU - Glencer, Alexa
AU  - Glencer A
FAU - Lahiri, Soumi
AU  - Lahiri S
FAU - Arbushites, Michael C
AU  - Arbushites MC
FAU - Scott, Janet
AU  - Scott J
FAU - Park, John W
AU  - Park JW
FAU - Hudis, Clifford
AU  - Hudis C
FAU - Nulsen, Ben
AU  - Nulsen B
FAU - Dickler, Maura N
AU  - Dickler MN
LA  - eng
SI  - ClinicalTrials.gov/NCT00444535
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20111224
PL  - Netherlands
TA  - Breast Cancer Res Treat
JT  - Breast cancer research and treatment
JID - 8111104
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Quinazolines)
RN  - 0VUA21238F (Lapatinib)
RN  - 2S9ZZM9Q9V (Bevacizumab)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Antibodies, Monoclonal, Humanized/administration & dosage
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
MH  - Bevacizumab
MH  - Breast Neoplasms/*drug therapy/metabolism/pathology
MH  - Disease-Free Survival
MH  - Female
MH  - *Gene Expression
MH  - Humans
MH  - Lapatinib
MH  - Middle Aged
MH  - Neoplasm Metastasis
MH  - Proportional Hazards Models
MH  - Quinazolines/administration & dosage
MH  - Receptor, ErbB-2/genetics/*metabolism
MH  - Treatment Outcome
PMC - PMC3397213
EDAT- 2011/12/27 06:00
MHDA- 2012/12/10 06:00
PMCR- 2011/12/24
CRDT- 2011/12/27 06:00
PHST- 2011/12/07 00:00 [received]
PHST- 2011/12/09 00:00 [accepted]
PHST- 2011/12/27 06:00 [entrez]
PHST- 2011/12/27 06:00 [pubmed]
PHST- 2012/12/10 06:00 [medline]
PHST- 2011/12/24 00:00 [pmc-release]
AID - 1918 [pii]
AID - 10.1007/s10549-011-1918-z [doi]
PST - ppublish
SO  - Breast Cancer Res Treat. 2012 Jul;134(1):13-20. doi: 10.1007/s10549-011-1918-z. 
      Epub 2011 Dec 24.