title: A neoadjuvant, randomized, open-label phase II trial of afatinib versus trastuzumab versus lapatinib in patients with locally advanced HER2-positive breast cancer.
abstract: BACKGROUND
  Chemotherapy is standard neoadjuvant treatment of LA BC. Patients with HER2-positive BC require targeted therapy. Trastuzumab and pertuzumab, which target HER2, with chemotherapy are approved as neoadjuvant therapy, however, treatments with different mechanisms of action might provide a broader range of activity. In this study we evaluated the efficacy and safety of the irreversible ErbB family blocker afatinib, versus trastuzumab or lapatinib in the neoadjuvant treatment of HER2-positive, LA BC.
  
  
  METHODS
  Treatment-naive, HER2-positive BC patients with stage IIIA, B, C or inflammatory disease were randomized 1:1:1 to daily afatinib (50 mg), lapatinib (1500 mg), or weekly trastuzumab (4 mg/kg loading dose, then 2 mg/kg/wk) for 6 weeks until surgery or follow-up neoadjuvant treatment. The primary end point was objective response rate according to Response Evaluation Criteria in Solid Tumors (version 1.0).
  
  
  RESULTS
  Recruitment was stopped early because of slow patient enrollment; 29 patients were randomized to afatinib (n = 10), lapatinib (n = 8), or trastuzumab (n = 11). Objective response was seen in 8 afatinib-, 6 lapatinib-, and 4 trastuzumab-treated patients. Eleven patients had stable disease (best response); 1 lapatinib- and 1 trastuzumab-treated patient had progressive disease. All 10 afatinib-treated patients experienced drug-related adverse events (commonly diarrhea, dermatitis acneiform, and paronychia) versus 6 of 8 lapatinib- (diarrhea and rash) and 5 of 11 trastuzumab-treated patients (vomiting and arthralgia).
  
  
  CONCLUSIONS
  Afatinib demonstrated clinical activity that compared favorably to trastuzumab and lapatinib for neoadjuvant treatment of HER2-positive BC, with a safety profile consistent with epidermal growth factor receptor tyrosine kinase inhibitors.
authors.affiliation: Baylor College of Medicine, Houston, TX. Electronic address: rimawi@bcm.edu.
authors.forename: Mothaffar F
authors.initials: MF
authors.lastname: Rimawi
authors.affiliation: CPCO - Centro de Pesquisas Clínicas em Oncologia, Cachoeiro de Itapemirim, Brazil.
authors.forename: Sabina B
authors.initials: SB
authors.lastname: Aleixo
authors.affiliation: Clinica Anglo Americana, Lima, Peru.
authors.forename: Ashley Alarcon
authors.initials: AA
authors.lastname: Rozas
authors.affiliation: Hospital Universitário de Brasília - Hub, Brasilia, Brazil.
authors.forename: João
authors.initials: J
authors.lastname: Nunes de Matos Neto
authors.affiliation: Hospital Moinhos de Vento, Porto Alegre, Brazil.
authors.forename: Maira
authors.initials: M
authors.lastname: Caleffi
authors.affiliation: Instituto de Tratamento do Câncer - ITC, Campo Grande, Brazil.
authors.forename: Alicardo Cesar
authors.initials: AC
authors.lastname: Figueira
authors.affiliation: Liga Norte Riograndense Contra O Câncer, Natal, Brazil.
authors.forename: Sulene Cunha
authors.initials: SC
authors.lastname: Souza
authors.affiliation: Universidade de Caxias do Sul Ipcem - Instituto de Pesquisas Clínicas Para Estudos Multicêntricos, Caxias do Sul, Brazil.
authors.forename: Andre B
authors.initials: AB
authors.lastname: Reiriz
authors.affiliation: Baylor College of Medicine, Houston, TX.
authors.forename: Carolina
authors.initials: C
authors.lastname: Gutierrez
authors.affiliation: Boehringer Ingelheim do Brasil QF Ltd, Santo Amaro, São Paulo.
authors.forename: Heloisa
authors.initials: H
authors.lastname: Arantes
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany.
authors.forename: Martina M
authors.initials: MM
authors.lastname: Uttenreuther-Fischer
authors.affiliation: Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria.
authors.forename: Flavio
authors.initials: F
authors.lastname: Solca
authors.affiliation: Baylor College of Medicine, Houston, TX.
authors.forename: C Kent
authors.initials: CK
authors.lastname: Osborne
mesh_terms: D000328:Adult; D000077716:Afatinib; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D017024:Chemotherapy, Adjuvant / Q000379:methods; D005260:Female; D006801:Humans; D000077341:Lapatinib; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D020360:Neoadjuvant Therapy / Q000379:methods; D009367:Neoplasm Staging; D011799:Quinazolines / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D000068878:Trastuzumab / Q000627:therapeutic use*
chemical_list: D000077716:Afatinib; D000970:Antineoplastic Agents; D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab
keywords: Anti-HER2 monoclonal antibody; EGFR tyrosine kinase inhibitor; ErbB family blocker; Locally advanced breast cancer; Phase II