Factors associated with clinical benefit from epidermal growth factor receptor inhibitors in recurrent and metastatic squamous cell carcinoma of the head and neck

Oral Oncol. 2009 Oct;45(10):e155-60. doi: 10.1016/j.oraloncology.2009.05.637. Epub 2009 Jul 7.


Single agent epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) have demonstrated reproducible response rates of 5-15% in treatment of squamous cell carcinomas of the head and neck (SCCHN). The subset of patients that benefits most from these agents remains unknown. We reviewed individual patient data from five clinical trials of erlotinib, lapatinib, or gefitinib to determine if there are clinical characteristics that are associated with clinical benefit defined as complete response (CR), partial response (PR), and stable disease (SD) >4months. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Three-hundred and nineteen subjects were included. Observed responses were: 1% CR, 6% PR, 24% SD >4months, 18% SD <4months, 45% progressive disease (PD), 7% not evaluable (NE). The median OS was 6.4months and the median PFS was 2.7months. The most common toxicities observed were rash (grade 1 in 37%, grade 2 in 33%, grade 3+ in 6%) and diarrhea (grade 1 in 30%, grade 2 in 10%, grade 3+ in 5%). Performance status (PS) (p=0.04), older age (p=0.02), and development of rash (p<0.01), diarrhea (p=0.03), or oral side effects (p=0.02) were independently associated with clinical benefit. Older age, better PS, and development of rash were associated with longer PFS and OS. Clinical parameters that appear to predict response to EGFR TKI include PS and age. EGFR mechanistic toxicities that develop during therapy are also highly associated with benefit and suggest a relationship between drug exposure and outcome.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / secondary
  • Disease-Free Survival
  • ErbB Receptors / antagonists & inhibitors*
  • Erlotinib Hydrochloride
  • Female
  • Gefitinib
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / pathology
  • Humans
  • Lapatinib
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Quinazolines / therapeutic use
  • Retrospective Studies
  • Treatment Outcome


  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Quinazolines
  • Lapatinib
  • Erlotinib Hydrochloride
  • ErbB Receptors
  • Protein-Tyrosine Kinases
  • Gefitinib