title: Lapatinib monotherapy in patients with HER2-overexpressing relapsed or refractory inflammatory breast cancer: final results and survival of the expanded HER2+ cohort in EGF103009, a phase II study.
abstract: BACKGROUND
  Inflammatory breast cancer is an aggressive and biologically distinct form with a higher frequency of HER2 overexpression than other breast cancers. For patients with resistance to conventional anthracycline or taxane and trastuzumab treatment, options are limited. Lapatinib, an oral reversible inhibitor of epidermal growth factor receptor tyrosine kinases, previously had a 50% response rate in a cohort of 30 patients with HER2-overexpressing (HER2+) recurrent or anthracycline-refractory inflammatory breast cancer. We aimed to assess efficacy of lapatinib in an expanded cohort of patients with relapsed or refractory HER2+ disease.
  
  
  METHODS
  From March, 2005, to September, 2007, 126 patients with relapsed or refractory HER2+ inflammatory breast cancer were treated with lapatinib 1500 mg once daily in a non-randomised, open-label, phase II study. Pretreatment tumour biopsies were done to verify pathological features of inflammatory breast cancer. Skin disease was assessed every 4 weeks, and response in sites of measurable locally advanced or metastatic disease were assessed by response evaluation in solid tumours (RECIST) criteria every 8 weeks. The primary aim was to assess combined objective response rate, by clinically evaluable skin disease criteria and RECIST, if applicable. Analyses were done by intention to treat; patients with missing data were treated as non-responders. This study is registered with ClinicalTrials.gov, number NCT00105950.
  
  
  RESULTS
  Clinical presentation and biomarker analysis showed a tumour molecular profile consistent with inflammatory breast cancer. No patients had complete response. 49 patients (39%; 95% CI 30-48) had partial response. Median progression-free survival was 14.6 weeks (95% CI 12.1-16.0), with median duration of response of 20.9 weeks (12.7-32.1). Likelihood of response to lapatinib was not affected by previous treatment with trastuzumab. 130 (92%) of 141 patients had at least one adverse event; 45 (32%) had serious adverse events, the most common were dyspnoea (eight patients) and pleural effusion (six). Five patients had fatal adverse events that were possibly treatment related.
  
  
  CONCLUSIONS
  Lapatinib monotherapy is a potentially effective treatment for relapsed or refractory HER2+ inflammatory breast cancer.
  
  
  BACKGROUND
  GlaxoSmithKline.
authors.affiliation: The Chaim Sheba Medical Center, Tel Hashomer, Israel. bella.kaufman@sheba.health.gov.il
authors.forename: Bella
authors.initials: B
authors.lastname: Kaufman
authors.forename: Maureen
authors.initials: M
authors.lastname: Trudeau
authors.forename: Ahmad
authors.initials: A
authors.lastname: Awada
authors.forename: Kimberly
authors.initials: K
authors.lastname: Blackwell
authors.forename: Thomas
authors.initials: T
authors.lastname: Bachelot
authors.forename: Vanessa
authors.initials: V
authors.lastname: Salazar
authors.forename: Michelle
authors.initials: M
authors.lastname: DeSilvio
authors.forename: Ronald
authors.initials: R
authors.lastname: Westlund
authors.forename: Tal
authors.initials: T
authors.lastname: Zaks
authors.forename: Neil
authors.initials: N
authors.lastname: Spector
authors.forename: Stephen
authors.initials: S
authors.lastname: Johnston
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D005260:Female; D006801:Humans; D000077341:Lapatinib; D008875:Middle Aged; D011799:Quinazolines / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D012008:Recurrence; D012871:Skin Diseases / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases