title: Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer.
abstract: BACKGROUND
  The anti-human epidermal growth factor receptor 2 (HER2) humanized monoclonal antibody trastuzumab improves the outcome in patients with HER2-positive metastatic breast cancer. However, most cases of advanced disease eventually progress. Pertuzumab, an anti-HER2 humanized monoclonal antibody that inhibits receptor dimerization, has a mechanism of action that is complementary to that of trastuzumab, and combination therapy with the two antibodies has shown promising activity and an acceptable safety profile in phase 2 studies involving patients with HER2-positive breast cancer.
  
  
  METHODS
  We randomly assigned 808 patients with HER2-positive metastatic breast cancer to receive placebo plus trastuzumab plus docetaxel (control group) or pertuzumab plus trastuzumab plus docetaxel (pertuzumab group) as first-line treatment until the time of disease progression or the development of toxic effects that could not be effectively managed. The primary end point was independently assessed progression-free survival. Secondary end points included overall survival, progression-free survival as assessed by the investigator, the objective response rate, and safety.
  
  
  RESULTS
  The median progression-free survival was 12.4 months in the control group, as compared with 18.5 months in the pertuzumab group (hazard ratio for progression or death, 0.62; 95% confidence interval, 0.51 to 0.75; P<0.001). The interim analysis of overall survival showed a strong trend in favor of pertuzumab plus trastuzumab plus docetaxel. The safety profile was generally similar in the two groups, with no increase in left ventricular systolic dysfunction; the rates of febrile neutropenia and diarrhea of grade 3 or above were higher in the pertuzumab group than in the control group.
  
  
  CONCLUSIONS
  The combination of pertuzumab plus trastuzumab plus docetaxel, as compared with placebo plus trastuzumab plus docetaxel, when used as first-line treatment for HER2-positive metastatic breast cancer, significantly prolonged progression-free survival, with no increase in cardiac toxic effects. (Funded by F. Hoffmann-La Roche/Genentech; ClinicalTrials.gov number, NCT00567190.).
authors.affiliation: Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA 02114, USA. jbaselga@partners.org
authors.forename: José
authors.initials: J
authors.lastname: Baselga
authors.forename: Javier
authors.initials: J
authors.lastname: Cortés
authors.forename: Sung-Bae
authors.initials: SB
authors.lastname: Kim
authors.forename: Seock-Ah
authors.initials: SA
authors.lastname: Im
authors.forename: Roberto
authors.initials: R
authors.lastname: Hegg
authors.forename: Young-Hyuck
authors.initials: YH
authors.lastname: Im
authors.forename: Laslo
authors.initials: L
authors.lastname: Roman
authors.forename: José Luiz
authors.initials: JL
authors.lastname: Pedrini
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Pienkowski
authors.forename: Adam
authors.initials: A
authors.lastname: Knott
authors.forename: Emma
authors.initials: E
authors.lastname: Clark
authors.forename: Mark C
authors.initials: MC
authors.lastname: Benyunes
authors.forename: Graham
authors.initials: G
authors.lastname: Ross
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Swain
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D000077143:Docetaxel; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors*; D043823:Taxoids / Q000008:administration & dosage* / Q000009:adverse effects; D000068878:Trastuzumab; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000077143:Docetaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D000068878:Trastuzumab; C485206:pertuzumab