title: Quality of life in hormone receptor-positive HER-2+ metastatic breast cancer patients during treatment with letrozole alone or in combination with lapatinib.
abstract: BACKGROUND
  A phase III trial compared lapatinib plus letrozole (L + Let) with letrozole plus placebo (Let) as first-line therapy for hormone receptor (HR)(+) metastatic breast cancer (MBC) patients. The primary endpoint of progression-free survival (PFS) in patients whose tumors were human epidermal growth factor receptor (HER)-2(+) was significantly longer for L + Let than for Let (8.2 months versus 3 months; p = .019). This analysis focuses on quality of life (QOL) in the HER-2(+) population.
  
  
  METHODS
  QOL was assessed at screening, every 12 weeks, and at withdrawal using the Functional Assessment of Cancer Therapy-Breast (FACT-B). Changes from baseline were analyzed and the proportions of patients achieving minimally important differences in QOL scores were compared. Additional exploratory analyses evaluated how QOL changes reflected tumor progression status.
  
  
  RESULTS
  Among the 1,286 patients randomized, 219 had HER-2(+) tumors. Baseline QOL scores were comparable in the two arms. Mean changes in QOL scores were generally stable over time for patients who stayed on study. The average change from baseline on the FACT-B total score in both arms was positive at all scheduled visits through week 48. There was no significant difference between the two treatment arms in the percentage of QOL responders.
  
  
  CONCLUSIONS
  The addition of lapatinib to letrozole led to a significantly longer PFS interval while maintaining QOL during treatment, when compared with letrozole alone, thus confirming the clinical benefit of the combination therapy in the HR(+) HER-2(+) MBC patient population. This all oral regimen provides an effective option in this patient population, delaying the need for chemotherapy and its accompanying side effects.
authors.affiliation: RTI Health Solutions, Research Triangle Park, North Carolina 27709-2194, USA. bsherrill@rti.org
authors.forename: Beth
authors.initials: B
authors.lastname: Sherrill
authors.forename: Mayur M
authors.initials: MM
authors.lastname: Amonkar
authors.forename: Bintu
authors.initials: B
authors.lastname: Sherif
authors.forename: Julie
authors.initials: J
authors.lastname: Maltzman
authors.forename: Lisa
authors.initials: L
authors.lastname: O'Rourke
authors.forename: Stephen
authors.initials: S
authors.lastname: Johnston
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000523:psychology; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000077341:Lapatinib; D000077289:Letrozole; D009570:Nitriles / Q000008:administration & dosage / Q000627:therapeutic use*; D011788:Quality of Life; D011799:Quinazolines / Q000008:administration & dosage*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D014230:Triazoles / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000077341:Lapatinib; D000077289:Letrozole; D009570:Nitriles; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D014230:Triazoles; C508053:ERBB2 protein, human
references.citation: Endocr Rev. 2008 Apr;29(2):217-33
references.pmid: 18216219
references.citation: Clin Cancer Res. 2004 Jun 1;10(11):3621-8
references.pmid: 15173068
references.citation: Br J Cancer. 2008 Sep 2;99(5):711-5
references.pmid: 18728660
references.citation: J Clin Oncol. 1997 Mar;15(3):974-86
references.pmid: 9060536
references.citation: Proc Natl Acad Sci U S A. 2006 May 16;103(20):7795-800
references.pmid: 16682622
references.citation: J Clin Oncol. 2009 Nov 20;27(33):5529-37
references.pmid: 19786670
references.citation: J Clin Oncol. 2005 Jul 1;23(19):4265-74
references.pmid: 15911866
references.citation: Clin Cancer Res. 2007 Mar 15;13(6):1648-55
references.pmid: 17363517
references.citation: Cancer. 1997 Oct 15;80(8 Suppl):1588-94
references.pmid: 9362426
references.citation: J Clin Oncol. 2009 Nov 20;27(33):5538-46
references.pmid: 19786658
references.citation: Eur J Cancer. 2001 Sep;37 Suppl 4:S9-15
references.pmid: 11597399
references.citation: J Clin Oncol. 2003 May 15;21(10):1967-72
references.pmid: 12743150
references.citation: Breast Cancer Res Treat. 2009 Oct;117(3):577-89
references.pmid: 19153829
references.citation: CA Cancer J Clin. 2009 Jul-Aug;59(4):225-49
references.pmid: 19474385
references.citation: Nature. 2008 Dec 4;456(7222):663-6
references.pmid: 19005469
references.citation: J Clin Oncol. 2004 Sep 1;22(17):3608-17
references.pmid: 15337811
references.citation: J Clin Epidemiol. 2004 Sep;57(9):898-910
references.pmid: 15504633
references.citation: Nat Rev Cancer. 2002 Aug;2(8):584-93
references.pmid: 12154351
references.citation: N Engl J Med. 2001 Mar 15;344(11):783-92
references.pmid: 11248153