title: Randomized phase II study of the anti-epidermal growth factor receptor monoclonal antibody cetuximab with cisplatin versus cisplatin alone in patients with metastatic triple-negative breast cancer.
abstract: Epidermal growth factor receptor is overexpressed in metastatic triple-negative breast cancers (mTNBCs), an aggressive subtype of breast cancer. Our randomized phase II study investigated cisplatin with or without cetuximab in this setting.
  
  
  
  Patients who had received no more than one previous chemotherapy regimen were randomly assigned on a 2:1 schedule to receive no more than six cycles of cisplatin plus cetuximab or cisplatin alone. Patients receiving cisplatin alone could switch to cisplatin plus cetuximab or cetuximab alone on disease progression. The primary end point was overall response rate (ORR). Secondary end points studied included progression-free survival (PFS), overall survival (OS), and safety profiles. Analyses included a significance level of α = .10 with no adjustments for multiplicity.
  
  
  
  The full analysis set comprised 115 patients receiving cisplatin plus cetuximab and 58 receiving cisplatin alone; 31 patients whose disease progressed on cisplatin alone switched to cetuximab-containing therapy. The ORR was 20% (95% CI, 13 to 29) with cisplatin plus cetuximab and 10% (95% CI, 4 to 21) with cisplatin alone (odds ratio, 2.13; 95% CI, 0.81 to 5.59; P = .11). Cisplatin plus cetuximab resulted in longer PFS compared with cisplatin alone (median, 3.7 v 1.5 months; hazard ratio [HR], 0.67; 95% CI, 0.47 to 0.97; P = .032). Corresponding median OS was 12.9 versus 9.4 months (HR, 0.82; 95% CI, 0.56 to 1.20; P = .31). Common grade 3/4 adverse events included acne-like rash, neutropenia, and fatigue.
  
  
  
  While the primary study end point was not met, adding cetuximab to cisplatin doubled the ORR and appeared to prolong PFS and OS, warranting further investigation in mTNBC.
authors.affiliation: Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. baselgaj@mskcc.org
authors.forename: José
authors.initials: J
authors.lastname: Baselga
authors.forename: Patricia
authors.initials: P
authors.lastname: Gómez
authors.forename: Richard
authors.initials: R
authors.lastname: Greil
authors.forename: Sofia
authors.initials: S
authors.lastname: Braga
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Climent
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Wardley
authors.forename: Bella
authors.initials: B
authors.lastname: Kaufman
authors.forename: Salomon M
authors.initials: SM
authors.lastname: Stemmer
authors.forename: António
authors.initials: A
authors.lastname: Pêgo
authors.forename: Arlene
authors.initials: A
authors.lastname: Chan
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Goeminne
authors.forename: Marie-Pascale
authors.initials: MP
authors.lastname: Graas
authors.forename: M John
authors.initials: MJ
authors.lastname: Kennedy
authors.forename: Eva Maria
authors.initials: EM
authors.lastname: Ciruelos Gil
authors.forename: Andreas
authors.initials: A
authors.lastname: Schneeweiss
authors.forename: Angela
authors.initials: A
authors.lastname: Zubel
authors.forename: Jutta
authors.initials: J
authors.lastname: Groos
authors.forename: Helena
authors.initials: H
authors.lastname: Melezínková
authors.forename: Ahmad
authors.initials: A
authors.lastname: Awada
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000068818:Cetuximab; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects; D016001:Confidence Intervals; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D066246:ErbB Receptors / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism; D011980:Receptors, Progesterone / Q000187:drug effects / Q000378:metabolism; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D066246:ErbB Receptors; D000068818:Cetuximab; D002945:Cisplatin