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

Ezra Eddy Wyssam Cohen*, Anna B. Halpern, Kristen Kasza, Masha Kocherginsky, Rosalyn Williams, Everett E. Vokes

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

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) >4 months. 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 >4 months, 18% SD <4 months, 45% progressive disease (PD), 7% not evaluable (NE). The median OS was 6.4 months and the median PFS was 2.7 months. 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.

Original languageEnglish (US)
Pages (from-to)e155-e160
JournalOral Oncology
Volume45
Issue number10
DOIs
StatePublished - Oct 2009

Keywords

  • Epidermal growth factor receptor
  • Head and neck squamous cell carcinoma
  • Meta-analysis
  • Tyrosine kinase inhibitor

ASJC Scopus subject areas

  • Oral Surgery
  • Oncology
  • Cancer Research

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