title: Efficacy of everolimus with exemestane versus exemestane alone in Asian patients with HER2-negative, hormone-receptor-positive breast cancer in BOLERO-2.
abstract: BACKGROUND
  The addition of mTOR inhibitor everolimus (EVE) to exemestane (EXE) was evaluated in an international, phase 3 study (BOLERO-2) in patients with hormone-receptor-positive (HR(+)) breast cancer refractory to letrozole or anastrozole. The safety and efficacy of anticancer treatments may be influenced by ethnicity (Sekine et al. in Br J Cancer 99:1757-62, 2008). Safety and efficacy results from Asian versus non-Asian patients in BOLERO-2 are reported.
  
  
  METHODS
  Patients were randomized (2:1) to 10 mg/day EVE + EXE or placebo (PBO) + EXE. Primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival, response rate, clinical benefit rate, and safety.
  
  
  RESULTS
  Of 143 Asian patients, 98 received EVE + EXE and 45 received PBO + EXE. Treatment with EVE + EXE significantly improved median PFS versus PBO + EXE among Asian patients by 38 % (HR = 0.62; 95 % CI, 0.41-0.94). Median PFS was also improved among non-Asian patients by 59 % (HR = 0.41; 95 % CI, 0.33-0.50). Median PFS duration among EVE-treated Asian patients was 8.48 versus 4.14 months for PBO + EXE, and 7.33 versus 2.83 months, respectively, in non-Asian patients. The most common grade 3/4 adverse events (stomatitis, anemia, elevated liver enzymes, hyperglycemia, and dyspnea) occurred at similar frequencies in Asian and non-Asian patients. Grade 1/2 interstitial lung disease occurred more frequently in Asian patients. Quality of life was similar between treatment arms in Asian patients.
  
  
  CONCLUSIONS
  Adding EVE to EXE provided substantial clinical benefit in both Asian and non-Asian patients with similar safety profiles. This combination represents an improvement in the management of postmenopausal women with HR(+)/HER2(-) advanced breast cancer progressing on nonsteroidal aromatase inhibitors, regardless of ethnicity.
authors: Department of Breast and Endocrine Surgery, Osaka University, Osaka, Japan, noguchi@onsurg.med.osaka-u.ac.jp.
authors: Shinzaburo
authors: S
authors: Noguchi
authors: Norikazu
authors: N
authors: Masuda
authors: Hiroji
authors: H
authors: Iwata
authors: Hirofumi
authors: H
authors: Mukai
authors: Jun
authors: J
authors: Horiguchi
authors: Puttisak
authors: P
authors: Puttawibul
authors: Vichien
authors: V
authors: Srimuninnimit
authors: Yutaka
authors: Y
authors: Tokuda
authors: Katsumasa
authors: K
authors: Kuroi
authors: Hirotaka
authors: H
authors: Iwase
authors: Hideo
authors: H
authors: Inaji
authors: Shozo
authors: S
authors: Ohsumi
authors: Woo-Chul
authors: WC
authors: Noh
authors: Takahiro
authors: T
authors: Nakayama
authors: Shinji
authors: S
authors: Ohno
authors: Yoshiaki
authors: Y
authors: Rai
authors: Byeong-Woo
authors: BW
authors: Park
authors: Ashok
authors: A
authors: Panneerselvam
authors: Mona
authors: M
authors: El-Hashimy
authors: Tetiana
authors: T
authors: Taran
authors: Tarek
authors: T
authors: Sahmoud
authors: Yoshinori
authors: Y
authors: Ito
mesh_terms: D000328:Adult; D000368:Aged; D000730:Androstadienes / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D044466:Asian People; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D000068338:Everolimus; D005260:Female; D006801:Humans; D008875:Middle Aged; D011788:Quality of Life; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D016896:Treatment Outcome
chemical_list: D000730:Androstadienes; D000068338:Everolimus; D018719:Erb-b2 Receptor Tyrosine Kinases; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human; C508053:ERBB2 protein, human; C056516:exemestane
references: Clin Cancer Res. 2005 Jul 15;11(14):5319-28
references: 16033851
references: Clin Cancer Res. 2004 Dec 1;10(23):8059-67
references: 15585641
references: Clin Med Insights Oncol. 2012;6:41-51
references: 22253554
references: Br J Cancer. 2008 Dec 2;99(11):1757-62
references: 18985035
references: J Natl Cancer Inst. 1993 Mar 3;85(5):365-76
references: 8433390
references: J Clin Invest. 2010 Jul;120(7):2406-13
references: 20530877
references: Am J Respir Crit Care Med. 2010 Aug 1;182(3):396-403
references: 20194812
references: Cancer. 2010 Sep 15;116(18):4256-65
references: 20549832
references: Breast. 2006 Oct;15(5):584-94
references: 16504510
references: Int J Epidemiol. 2005 Apr;34(2):405-12
references: 15737977
references: Ann Oncol. 2007 Aug;18(8):1323-8
references: 17693645
references: Jpn J Clin Oncol. 2012 May;42(5):442-6
references: 22438405
references: J Natl Cancer Inst. 2000 Feb 2;92(3):205-16
references: 10655437
references: J Clin Oncol. 2010 Apr 10;28(11):1904-10
references: 20231677
references: N Engl J Med. 2012 Feb 9;366(6):520-9
references: 22149876
references: Breast Cancer Res. 2012 Oct 26;14(5):R138
references: 23102376
references: Jpn J Clin Oncol. 2010 Jan;40(1):17-23
references: 19783551
references: Cancer Sci. 2008 Oct;99(10):1992-2003
references: 19016759
references: Ann Acad Med Singap. 2011 Aug;40(8):356-61
references: 22065001
references: Eur J Cancer. 2011 Jun;47(9):1287-98
references: 21481584
references: Annu Rev Pharmacol Toxicol. 2001;41:815-50
references: 11264478
references: Jpn J Clin Oncol. 2011 Jan;41(1):17-24
references: 20965941