title: Pattern of rash, diarrhea, and hepatic toxicities secondary to lapatinib and their association with age and response to neoadjuvant therapy: analysis from the NeoALTTO trial.
abstract: We investigated the pattern of rash, diarrhea, and hepatic adverse events (AEs) secondary to lapatinib and their association with age and pathologic complete response (pCR) in the Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimisation (NeoALLTO) phase III trial.
  
  
  
  Patients with HER2-positive early breast cancer were randomly assigned to receive lapatinib (Arm A), trastuzumab (Arm B), or their combination (Arm C) for 6 weeks followed by the addition of paclitaxel for 12 weeks before surgery. We investigated the frequency and time to developing each AE according to age (≤ 50 v > 50 years) and their association with pCR in a logistic regression model adjusted for age, hormone receptors, tumor size, nodal status, planned breast surgery, completion of lapatinib administration, and treatment arm.
  
  
  
  Only patients randomly assigned to arms A and C were eligible (n = 306). Younger patients (≤ 50 years) experienced significantly more rash compared with older patients (74.4% v 47.9%; P < .0001). Diarrhea and hepatic AEs were observed in 78.8% and 41.2% of patients, respectively, with no differences in rate or severity or time of onset according to age. Early rash (ie, before starting paclitaxel) was independently associated with a higher chance of pCR, mainly in patients older than 50 years (odds ratio [OR] = 3.76; 95% CI, 1.69 to 8.34) but not in those ≤ 50 years (OR = 0.92; 95% CI, 0.45 to 1.88; P for interaction = .01). No significant association was observed between pCR and diarrhea or hepatic AEs.
  
  
  
  Our results indicate that the frequency and clinical relevance of lapatinib-related rash is largely dependent on patient age.
authors.affiliation: Jose Baselga, Memorial Sloan-Kettering Cancer Center, NY; James G. Greger Jr, GlaxoSmithKline, Collegeville, PA; Hatem A. Azim Jr, Martine Piccart, Evandro de Azambuja, BrEAST Data Centre, Institut Jules Bordet, Université Libre de Bruxelles; Phuong Dinh, Breast International Group, Brussels; Peter Vuylsteke, Sint-Elisabeth Hospital, Namur, Belgium; Dominique Agbor-tarh, Ian Bradbury, Frontier Science, Kincraig, Kingussie, Scotland; Ian Smith, Royal Marsden Hospital, and Institute of Cancer Research, London, United Kingdom; Serena Di Cosimo, IRCCS Fondazione Instituto Nazionale dei Tumori, Milan, Italy; Serena Di Cosimo, SOLTI Breast Cancer Research Group, Barcelona, Spain; Christian Jackisch, Kilinikum Offenbach, Offenbach; Bahriye Aktas, Kliniken Essen-Mitte, Evang, Essen; Holger Eidtmann, University Hospital Kiel, Kiel, Germany; Sung-Bae Kim, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; Chiun-Sheng Huang, National Taiwan University Hospital; Ruey Kuen Hsieh, Mackey Memorial Hospital, Taipei, Taiwan; and Lydia Dreosti, University of Pretoria, Pretoria, South Africa.
authors.forename: Hatem A
authors.initials: HA
authors.lastname: Azim
authors.forename: Dominique
authors.initials: D
authors.lastname: Agbor-Tarh
authors.forename: Ian
authors.initials: I
authors.lastname: Bradbury
authors.forename: Phuong
authors.initials: P
authors.lastname: Dinh
authors.forename: Jose
authors.initials: J
authors.lastname: Baselga
authors.forename: Serena
authors.initials: S
authors.lastname: Di Cosimo
authors.forename: James G
authors.initials: JG
authors.lastname: Greger
authors.forename: Ian
authors.initials: I
authors.lastname: Smith
authors.forename: Christian
authors.initials: C
authors.lastname: Jackisch
authors.forename: Sung-Bae
authors.initials: SB
authors.lastname: Kim
authors.forename: Bahriye
authors.initials: B
authors.lastname: Aktas
authors.forename: Chiun-Sheng
authors.initials: CS
authors.lastname: Huang
authors.forename: Peter
authors.initials: P
authors.lastname: Vuylsteke
authors.forename: Ruey Kuen
authors.initials: RK
authors.lastname: Hsieh
authors.forename: Lydia
authors.initials: L
authors.lastname: Dreosti
authors.forename: Holger
authors.initials: H
authors.lastname: Eidtmann
authors.forename: Martine
authors.initials: M
authors.lastname: Piccart
authors.forename: Evandro
authors.initials: E
authors.lastname: de Azambuja
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D017024:Chemotherapy, Adjuvant; D003967:Diarrhea / Q000139:chemically induced*; D004334:Drug Administration Schedule; D003875:Drug Eruptions / Q000209:etiology*; D005260:Female; D006801:Humans; D015994:Incidence; D000077341:Lapatinib; D016015:Logistic Models; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D017239:Paclitaxel / Q000008:administration & dosage; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D013997:Time Factors; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000077341:Lapatinib; D017239:Paclitaxel; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human