title: Preoperative chemotherapy plus trastuzumab, lapatinib, or both in human epidermal growth factor receptor 2-positive operable breast cancer: results of the randomized phase II CHER-LOB study.
abstract: OBJECTIVE
  This is a noncomparative, randomized, phase II trial of preoperative taxane-anthracycline in combination with trastuzumab, lapatinib, or combined trastuzumab plus lapatinib in patients with human epidermal growth factor receptor 2 (HER2) -positive, stage II to IIIA operable breast cancer. The primary aim was to estimate the percentage of pathologic complete response (pCR; no invasive tumor in breast and axillary nodes).
  
  
  METHODS
  In the three arms, chemotherapy consisted of weekly paclitaxel (80 mg/m(2)) for 12 weeks followed by fluorouracil, epirubicin, and cyclophosphamide for four courses every 3 weeks. The patients randomly assigned to arm A received a 4-mg loading dose of trastuzumab followed by 2 mg weekly; in arm B patients received lapatinib 1,500 mg orally (PO) daily; and in arm C, patients received trastuzumab and lapatinib 1,000 mg PO daily.
  
  
  RESULTS
  A total of 121 patients were randomly assigned. Diarrhea and dermatologic and hepatic toxicities were observed more frequently in patients receiving lapatinib. No episodes of congestive heart failure were observed. The rates of breast-conserving surgery were 66.7%, 57.9%, and 68.9% in arms A, B and C, respectively. The pCR rates were 25% (90% CI, 13.1% to 36.9%) in arm A, 26.3% (90% CI, 14.5% to 38.1%) in arm B, and 46.7% (90% CI, 34.4% to 58.9%) in arm C (exploratory P = .019).
  
  
  CONCLUSIONS
  The primary end point of the study was met, with a relative increase of 80% in the pCR rate achieved with chemotherapy plus trastuzumab and lapatinib compared with chemotherapy plus either trastuzumab or lapatinib. These data add further evidence supporting the superiority of a dual-HER2 inhibition for the treatment of HER2-positive breast cancer.
authors.affiliation: Department of Oncology, Hematology and Respiratory Diseases, University Hospital, via del Pozzo 71, 41100 Modena, Italy. conte.pierfranco@unimore.it
authors.forename: Valentina
authors.initials: V
authors.lastname: Guarneri
authors.forename: Antonio
authors.initials: A
authors.lastname: Frassoldati
authors.forename: Alberto
authors.initials: A
authors.lastname: Bottini
authors.forename: Katia
authors.initials: K
authors.lastname: Cagossi
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Bisagni
authors.forename: Samanta
authors.initials: S
authors.lastname: Sarti
authors.forename: Alberto
authors.initials: A
authors.lastname: Ravaioli
authors.forename: Luigi
authors.initials: L
authors.lastname: Cavanna
authors.forename: Giovanni
authors.initials: G
authors.lastname: Giardina
authors.forename: Antonino
authors.initials: A
authors.lastname: Musolino
authors.forename: Michael
authors.initials: M
authors.lastname: Untch
authors.forename: Laura
authors.initials: L
authors.lastname: Orlando
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Artioli
authors.forename: Corrado
authors.initials: C
authors.lastname: Boni
authors.forename: Daniele Giulio
authors.initials: DG
authors.lastname: Generali
authors.forename: Patrizia
authors.initials: P
authors.lastname: Serra
authors.forename: Michela
authors.initials: M
authors.lastname: Bagnalasta
authors.forename: Luca
authors.initials: L
authors.lastname: Marini
authors.forename: Federico
authors.initials: F
authors.lastname: Piacentini
authors.forename: Roberto
authors.initials: R
authors.lastname: D'Amico
authors.forename: Pierfranco
authors.initials: P
authors.lastname: Conte
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000601:surgery; D003520:Cyclophosphamide / Q000008:administration & dosage; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077341:Lapatinib; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D017239:Paclitaxel / Q000008:administration & dosage; D011799:Quinazolines / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D003520:Cyclophosphamide; D015251:Epirubicin; D005472:Fluorouracil; D000077341:Lapatinib; D017239:Paclitaxel; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases