title: Dual Block with Lapatinib and Trastuzumab Versus Single-Agent Trastuzumab Combined with Chemotherapy as Neoadjuvant Treatment of HER2-Positive Breast Cancer: A Meta-analysis of Randomized Trials.
abstract: OBJECTIVE
  (Neo)adjuvant treatment with chemotherapy plus trastuzumab reduces recurrence and death risk in HER2-positive (HER2(+)) breast cancer. Randomized trials assessed HER2 dual block by adding lapatinib to trastuzumab and chemotherapy in the neoadjuvant setting using pathologic complete response (pCR) as the outcome measure. We conducted a meta-analysis of randomized trials testing neoadjuvant dual block with lapatinib and trastuzumab versus trastuzumab alone in HER2(+) breast cancer.
  
  
  METHODS
  Trials were identified by Medline (PubMed), ISI Web of Science (Science Citation Index Expanded), Embase, Cochrane library, and reference lists of published studies, review articles, editorials, and by hand-searched reports from major cancer meeting reports.
  
  
  RESULTS
  Six randomized trials including 1,155 patients were identified, of whom 483 (41.8%) were hormone receptor-negative, 672 (58.2%) hormone receptor-positive, 534 (46.2%) received taxanes alone, and 621 (53.8%) anthracyclines plus taxanes or the docetaxel-carboplatin regimen. Overall, the dual block was associated with a significant 13% absolute improvement in pCR rate compared with single-agent trastuzumab (summary risk difference, SRD 0.13; 95% CI, 0.08-0.19). The activity was greater in hormone receptor-negative patients who received chemotherapy with taxanes alone (SRD 0.25; 95% CI, 0.13-0.37), compared to hormone receptor-positive or hormone receptor-negative disease treated with anthracyclines plus taxanes or the docetaxel-carboplatin regimen (SRD 0.09; 95% CI, 0.02-0.15; Pinteraction = 0.05).
  
  
  CONCLUSIONS
  On the basis of ΔpCR data, the dual block with trastuzumab and lapatinib plus chemotherapy is a very active treatment only in HER2(+) and hormone receptor-negative breast cancer treated with taxane monochemotherapy. Clin Cancer Res; 22(18); 4594-603. ©2016 AACR.
authors.affiliation: Medical Oncology Unit, E.O. Ospedali Galliera, Genova, Italy. matteo.clavarezza@galliera.it.
authors.forename: Matteo
authors.initials: M
authors.lastname: Clavarezza
authors.affiliation: Clinical Trial and Biostatistical Unit, Scientific Direction, E.O. Ospedali Galliera, Genova, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Puntoni
authors.affiliation: Medical Oncology Unit, E.O. Ospedali Galliera, Genova, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Gennari
authors.affiliation: Medical Oncology Unit, E.O. Ospedali Galliera, Genova, Italy. Public Health Agency, Liguria Region, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Paleari
authors.affiliation: Medical Oncology Unit, E.O. Ospedali Galliera, Genova, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Provinciali
authors.affiliation: Medical Oncology Unit, E.O. Ospedali Galliera, Genova, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: D'Amico
authors.affiliation: Medical Oncology Unit, E.O. Ospedali Galliera, Genova, Italy. Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom.
authors.forename: Andrea
authors.initials: A
authors.lastname: DeCensi
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D000077341:Lapatinib; D058990:Molecular Targeted Therapy; D020360:Neoadjuvant Therapy; D011799:Quinazolines / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000068878:Trastuzumab / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab