PMID- 24101324
OWN - NLM
STAT- MEDLINE
DCOM- 20140527
LR  - 20211021
IS  - 1573-7217 (Electronic)
IS  - 0167-6806 (Print)
IS  - 0167-6806 (Linking)
VI  - 141
IP  - 3
DP  - 2013 Oct
TI  - A phase 2 study of everolimus combined with trastuzumab and paclitaxel in 
      patients with HER2-overexpressing advanced breast cancer that progressed during 
      prior trastuzumab and taxane therapy.
PG  - 437-46
LID - 10.1007/s10549-013-2689-5 [doi]
AB  - Increased activation of the PI3K/Akt/mTOR pathway is a common factor in putative 
      mechanisms of trastuzumab resistance, resulting in dysregulation of cell 
      migration, growth, proliferation, and survival. Data from preclinical and phase 
      1/2 clinical studies suggest that adding everolimus (an oral mTOR inhibitor) to 
      trastuzumab plus chemotherapy may enhance the efficacy of, and restore 
      sensitivity to, trastuzumab-based therapy. In this phase 2 multicenter study, 
      adult patients with HER2-positive advanced breast cancer resistant to trastuzumab 
      and pretreated with a taxane received everolimus 10 mg/day in combination with 
      paclitaxel (80 mg/m(2) days 1, 8, and 15 every 4 weeks) and trastuzumab (4 mg/kg 
      loading dose followed by 2 mg/kg weekly), administered in 28-day cycles. 
      Endpoints included overall response rate (ORR), progression-free survival (PFS), 
      overall survival (OS), and safety. Fifty-five patients were enrolled; one 
      remained on study treatment at the time of data cutoff. The median number of 
      prior chemotherapy lines for advanced disease was 3.5 (range 1-11). The ORR was 
      21.8 %, the clinical benefit rate was 36.4 %, the median PFS estimate was 
      5.5 months (95 % confidence interval [CI]: 4.99-7.69 months), and the median OS 
      estimate was 18.1 months (95 % CI: 12.85-24.11 months). Hematologic grade 3/4 
      adverse events (AEs) included neutropenia (25.5 % grade 3, 3.6 % grade 4), anemia 
      (7.3 % grade 3), and thrombocytopenia (5.5 % grade 3, 1.8 % grade 4). 
      Nonhematologic grade 3/4 AEs included stomatitis (20.0 %), diarrhea (5.5 %), 
      vomiting (5.5 %), fatigue (5.5 %), and pneumonia (5.5 %), all grade 3. These 
      findings suggest that the combination of everolimus plus trastuzumab and 
      paclitaxel is feasible, with promising activity in patients with highly resistant 
      HER2-positive advanced breast cancer. This combination is currently under 
      investigation in the BOLERO-1 phase 3 trial.
FAU - Hurvitz, Sara A
AU  - Hurvitz SA
AD  - Department of Medicine, Hematology/Oncology, UCLA Jonsson Comprehensive Cancer 
      Center, 10945 Le Conte Avenue, PVUB Suite 3360, Los Angeles, CA, 90095, USA, 
      shurvitz@mednet.ucla.edu.
FAU - Dalenc, Florence
AU  - Dalenc F
FAU - Campone, Mario
AU  - Campone M
FAU - O'Regan, Ruth M
AU  - O'Regan RM
FAU - Tjan-Heijnen, Vivianne C
AU  - Tjan-Heijnen VC
FAU - Gligorov, Joseph
AU  - Gligorov J
FAU - Llombart, Antonio
AU  - Llombart A
FAU - Jhangiani, Haresh
AU  - Jhangiani H
FAU - Mirshahidi, Hamid R
AU  - Mirshahidi HR
FAU - Tan-Chiu, Elizabeth
AU  - Tan-Chiu E
FAU - Miao, Sara
AU  - Miao S
FAU - El-Hashimy, Mona
AU  - El-Hashimy M
FAU - Lincy, Jeremie
AU  - Lincy J
FAU - Taran, Tetiana
AU  - Taran T
FAU - Soria, Jean-Charles
AU  - Soria JC
FAU - Sahmoud, Tarek
AU  - Sahmoud T
FAU - Andre, Fabrice
AU  - Andre F
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131008
PL  - Netherlands
TA  - Breast Cancer Res Treat
JT  - Breast cancer research and treatment
JID - 8111104
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Taxoids)
RN  - 9HW64Q8G6G (Everolimus)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - P188ANX8CK (Trastuzumab)
RN  - P88XT4IS4D (Paclitaxel)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antibodies, Monoclonal, Humanized/administration & dosage
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Breast Neoplasms/*drug therapy/metabolism/mortality/pathology
MH  - Disease Progression
MH  - Disease-Free Survival
MH  - Everolimus
MH  - Female
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Middle Aged
MH  - Neoplasm Staging
MH  - Paclitaxel/administration & dosage
MH  - Receptor, ErbB-2/*metabolism
MH  - Sirolimus/administration & dosage/analogs & derivatives
MH  - Taxoids/administration & dosage
MH  - Trastuzumab
MH  - Treatment Failure
PMC - PMC3824346
EDAT- 2013/10/09 06:00
MHDA- 2014/05/28 06:00
PMCR- 2013/10/08
CRDT- 2013/10/09 06:00
PHST- 2013/06/28 00:00 [received]
PHST- 2013/08/28 00:00 [accepted]
PHST- 2013/10/09 06:00 [entrez]
PHST- 2013/10/09 06:00 [pubmed]
PHST- 2014/05/28 06:00 [medline]
PHST- 2013/10/08 00:00 [pmc-release]
AID - 2689 [pii]
AID - 10.1007/s10549-013-2689-5 [doi]
PST - ppublish
SO  - Breast Cancer Res Treat. 2013 Oct;141(3):437-46. doi: 10.1007/s10549-013-2689-5. 
      Epub 2013 Oct 8.