title: Phase II study of cetuximab as first-line single-drug therapy in patients with unresectable squamous cell carcinoma of the skin.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of cetuximab, a monoclonal antibody that inhibits the epidermal growth factor receptor (EGFR), as a first-line monotherapy in patients with unresectable squamous cell carcinoma of the skin (SCCS).
  
  
  METHODS
  Thirty-six patients received cetuximab (initial dose of 400 mg/m(2) followed by subsequent weekly doses of 250 mg/m(2)) for at least 6 weeks with a 48-week follow-up. The primary end point was the disease control rate (DCR) at 6 weeks (according to Response Evaluation Criteria in Solid Tumors [RECIST] criteria). Secondary end points included best response rate, overall survival, progression-free survival (PFS), and toxicity assessment. Association of treatment efficacy with RAS mutations or FcγR genotypes was investigated.
  
  
  RESULTS
  Median age of the study population was 79 years. DCR at 6 weeks was obtained in 25 of 36 patients (69%; 95% CI, 52% to 84%) of the intention-to-treat population. The best responses were eight partial responses and two complete responses. There were no cetuximab-related deaths. There were three related serious adverse events: two grade 4 infusion reactions and one grade 3 interstitial pneumopathy. Grade 1 to 2 acne-like rash occurred in 78% of patients and was associated with prolonged PFS. One HRAS mutation was identified. Combined FcγRIIa-131H/H and/or FcγRIIIa-158V/V polymorphisms were not associated with the clinical outcomes.
  
  
  CONCLUSIONS
  As a first-line treatment in patients with unresectable SCCS, cetuximab achieved 69% DCR. A randomized phase III trial is warranted to confirm that cetuximab may be considered as a therapeutic option especially in elderly patients. The low frequency of RAS mutations in SCCS makes SCCS tumors attractive for EGFR inhibition.
authors.affiliation: Hôpital Bichat, Service de Dermatologie, 46 rue Henri Huchard, Paris, cedex 75877, France. eve.maubec@bch.aphp.fr
authors.forename: Eve
authors.initials: E
authors.lastname: Maubec
authors.forename: Peter
authors.initials: P
authors.lastname: Petrow
authors.forename: Isabelle
authors.initials: I
authors.lastname: Scheer-Senyarich
authors.forename: Pierre
authors.initials: P
authors.lastname: Duvillard
authors.forename: Ludovic
authors.initials: L
authors.lastname: Lacroix
authors.forename: Julien
authors.initials: J
authors.lastname: Gelly
authors.forename: Agnès
authors.initials: A
authors.lastname: Certain
authors.forename: Xavier
authors.initials: X
authors.lastname: Duval
authors.forename: Béatrice
authors.initials: B
authors.lastname: Crickx
authors.forename: Valérie
authors.initials: V
authors.lastname: Buffard
authors.forename: Nicole
authors.initials: N
authors.lastname: Basset-Seguin
authors.forename: Pierre
authors.initials: P
authors.lastname: Saez
authors.forename: Anne-Bénédicte
authors.initials: AB
authors.lastname: Duval-Modeste
authors.forename: Henri
authors.initials: H
authors.lastname: Adamski
authors.forename: Sandrine
authors.initials: S
authors.lastname: Mansard
authors.forename: Florent
authors.initials: F
authors.lastname: Grange
authors.forename: Anne
authors.initials: A
authors.lastname: Dompmartin
authors.forename: Sandrine
authors.initials: S
authors.lastname: Faivre
authors.forename: France
authors.initials: F
authors.lastname: Mentré
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Avril
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000556:secondary / Q000601:surgery; D000068818:Cetuximab; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068818:Cetuximab