title: Cetuximab for the treatment of advanced bronchioloalveolar carcinoma (BAC): an Eastern Cooperative Oncology Group phase II study (ECOG 1504).
abstract: OBJECTIVE
  Inhibitors of the epidermal growth factor receptor (EGFR) tyrosine kinase have demonstrated modest anticancer activity in advanced bronchioloalveolar carcinoma (BAC). We conducted a phase II study to evaluate cetuximab for the treatment of advanced BAC.
  
  
  METHODS
  Patients with advanced-stage pure BAC or adenocarcinoma with BAC features, fewer than two prior chemotherapy regimens, and Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 were eligible. Those with prior EGFR inhibitor therapy were excluded. Cetuximab was given as a weekly intravenous infusion at 250 mg/m(2) after an initial loading dose of 400 mg/m(2) in week 1. The primary end point was determination of response rate. EGFR and KRAS mutations were evaluated by pyrosequencing.
  
  
  RESULTS
  Seventy-two patients were enrolled and 68 met eligibility requirements. Characteristics of patients included median age, 71 years; sex, 57% females; PS 0 or 1, 88% of patients; and smoking status, 19% never-smokers. Central pathology review confirmed the diagnosis in 45 of 49 available specimens. Approximately 50% of patients received more than two cycles of therapy (> 8 weeks). Skin rash was the most common toxicity (grade 3, 15%). The confirmed response rate was 7%, and stable disease was observed in 35%. The median survival and progression-free survival were 13 and 3.3 months, respectively. Only one of the six patients with an EGFR mutation and one of the seven patients with a KRAS mutation had a partial response.
  
  
  CONCLUSIONS
  Cetuximab was associated with modest efficacy in patients with advanced BAC, despite a low response rate. EGFR and KRAS mutations were not predictive of response to cetuximab.
authors.affiliation: Emory University, Winship Cancer Institute, Atlanta, GA, USA. suresh.ramalingam@emory.edu
authors.forename: Suresh S
authors.initials: SS
authors.lastname: Ramalingam
authors.forename: Ju-Whei
authors.initials: JW
authors.lastname: Lee
authors.forename: Chandra P
authors.initials: CP
authors.lastname: Belani
authors.forename: Seena C
authors.initials: SC
authors.lastname: Aisner
authors.forename: Jill
authors.initials: J
authors.lastname: Kolesar
authors.forename: Craig
authors.initials: C
authors.lastname: Howe
authors.forename: Mario R
authors.initials: MR
authors.lastname: Velasco
authors.forename: Joan H
authors.initials: JH
authors.lastname: Schiller
mesh_terms: D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000188:drug therapy* / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000068818:Cetuximab; D005260:Female; D049452:Green Fluorescent Proteins / Q000037:antagonists & inhibitors; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D000068818:Cetuximab