title: A Phase II Randomized Study of Lapatinib Combined With Capecitabine, Vinorelbine, or Gemcitabine in Patients With HER2-Positive Metastatic Breast Cancer With Progression After a Taxane (Latin American Cooperative Oncology Group 0801 Study).
abstract: BACKGROUND
  Novel targeted agents and combinations have become available in multiple lines of treatment for human epidermal growth factor receptor 2-positive (HER2(+)) metastatic breast cancer (MBC). In this context, alternatives to the lapatinib (L) and capecitabine (C) regimen, evaluating L combined with other cytotoxic drugs, are warranted.
  
  
  METHODS
  In the present phase II, multicenter study, patients with HER2(+) MBC with progression after taxane were randomized between L, 1250 mg, combined with C, 2000 mg/m(2) on days 1 to 14 (LC), vinorelbine (V), 25 mg/m(2) on days 1 and 8 (LV), or gemcitabine (G), 1000 mg/m(2) on days 1 and 8 (LG), every 21 days. The primary endpoint was the overall response rate.
  
  
  RESULTS
  A total of 142 patients were included from 2009 to 2012. No differences were found in the patient baseline characteristics. The median age was 51 years, 69% were postmenopausal, 32% had liver metastasis, 57% were hormone receptor negative, and 48% had been previously treated with trastuzumab. The overall response rate was 49% (95% confidence interval [CI], 34.8%-63.4%), 56% (95% CI, 40%-70.4%), and 41% (95% CI, 27%-56.8%) in the LC, LV, and LG groups, respectively. The median progression-free survival was 9 months in the LC arm and 7 months in the other 2 arms (P = .28). The most common grade 3 and 4 adverse events were hand-foot syndrome (18%), diarrhea (6%), and increased alanine aminotransferase/aspartate aminotransferase (4%) in the LC arm; neutropenia (36%), diarrhea (9%), and febrile neutropenia (6%) in the LV arm; and neutropenia (47%), alanine aminotransferase/aspartate aminotransferase (13%), and rash (4%) in the LG arm.
  
  
  CONCLUSIONS
  LV and LG seem to be active combinations in patients with HER2(+) MBC after taxane failure. The overall toxicity was manageable in all regimens.
authors.affiliation: Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru.
authors.forename: Henry L
authors.initials: HL
authors.lastname: Gómez
authors.affiliation: Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru.
authors.forename: Silvia
authors.initials: S
authors.lastname: Neciosup
authors.affiliation: Instituto Brasileiro de Controle do Câncer, São Paulo, São Paulo, Brazil.
authors.forename: Célia
authors.initials: C
authors.lastname: Tosello
authors.affiliation: Instituto do Câncer do Estado de São Paulo, Universidade de São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Max
authors.initials: M
authors.lastname: Mano
authors.affiliation: Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
authors.forename: José
authors.initials: J
authors.lastname: Bines
authors.affiliation: Fundação Doutor Amaral Carvalho, Jaú, Brazil.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Ismael
authors.affiliation: Instituto de Ensino e Pesquisa São Lucas, Santo André, Brazil.
authors.forename: Patrícia X
authors.initials: PX
authors.lastname: Santi
authors.affiliation: Instituto de Ensino e Pesquisa São Lucas, Santo André, Brazil.
authors.forename: Hélio
authors.initials: H
authors.lastname: Pinczowski
authors.affiliation: Centro de Pesquisas Oncológicas de Santa Catarina, Florianópolis, Brazil.
authors.forename: Yeni
authors.initials: Y
authors.lastname: Nerón
authors.affiliation: Hospital A.C. Camargo, São Paulo, Brazil.
authors.forename: Marcello
authors.initials: M
authors.lastname: Fanelli
authors.affiliation: Centro Oncológico de Rosário, Rosário, Argentina.
authors.forename: Luis
authors.initials: L
authors.lastname: Fein
authors.affiliation: Clínica Amo, Salvador, Brazil.
authors.forename: Carlos
authors.initials: C
authors.lastname: Sampaio
authors.affiliation: Investigaciones Clínicas Ciudad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Lerzo
authors.affiliation: Fundación Centro Oncológico de Integración Regional, Mendoza, Argentina.
authors.forename: Adolfo
authors.initials: A
authors.lastname: Capó
authors.affiliation: Centro San Roque, Tucumán, Argentina.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Zarba
authors.affiliation: ISIS Clínica Especializada, Santa Fé, Argentina.
authors.forename: César
authors.initials: C
authors.lastname: Blajman
authors.affiliation: CER Instituto Médico, Buenos Aires, Argentina.
authors.forename: Mirta S
authors.initials: MS
authors.lastname: Varela
authors.affiliation: Latin American Cooperative Oncology Group (LACOG), Porto Alegre, Brazil.
authors.forename: Jeovany
authors.initials: J
authors.lastname: Martínez-Mesa
authors.affiliation: Latin American Cooperative Oncology Group (LACOG), Porto Alegre, Brazil. Electronic address: gustavo.werutsky@lacog.org.br.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Werutsky
authors.affiliation: Pontifical Catholic University of Rio Grande do Sul School of Medicine, Hospital São Lucas, Porto Alegre, Brazil.
authors.forename: Carlos H
authors.initials: CH
authors.lastname: Barrios
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality; D000069287:Capecitabine / Q000008:administration & dosage / Q000009:adverse effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018450:Disease Progression; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D000077341:Lapatinib; D008875:Middle Aged; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D016879:Salvage Therapy / Q000379:methods*; D043823:Taxoids / Q000627:therapeutic use; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000077235:Vinorelbine; D055815:Young Adult; D000093542:Gemcitabine
chemical_list: D000069287:Capecitabine; D003841:Deoxycytidine; D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D014747:Vinblastine; D000077235:Vinorelbine; D000093542:Gemcitabine; C508053:ERBB2 protein, human
keywords: Chemotherapy; Human epidermal growth factor receptor 2-positive; Lapatinib; Metastatic breast cancer; Treatment outcome