Prognostic factors for clinical benefit after epidermal growth factor receptor (EGFR) directed therapy in squamous cell carcinomas of the head and neck (SCCHN)

Abstract

6025 Background: Single agent EGFR tyrosine kinase inhibitors (TKI) have demonstrated reproducible response rates of 5–15% in treatment of SCCHN. The subset of patients that benefits most from these agents remains unknown. We undertook a review of data from 5 clinical trials administering EGFR TKI in order to determine if there are clinical characteristics that are associated with response or benefit. Methods: We reviewed individual patient data from 5 clinical trials of erlotinib, lapatinib, or gefitinib. The primary endpoint was association of clinical variables with clinical benefit, defined as response (CR or PR) and stable disease (SD) >4 months. Secondary correlative endpoints included progression-free survival (PFS) and overall survival (OS). Logistic regression and Cox proportional hazard models were used to conduct univariate and multivariate analysis. Results: 319 subjects were included in the analysis with a median age of 59 years, 79% male. Disease status at start of therapy was local only in 43%, metastatic only in 29%, and both in 27%. Performance status (PS) was 0 in 25%, 1 in 62%, and 2 in 13%. Observed responses were: 1% CR, 6% PR, 24% SD >4 mo, 18 % SD3 in 6%) and diarrhea (grade 1 in 30%, grade 2 in 10%, grade 3 in 5%). Lower PS (p=0.06, OR (0/2)=3.1), age 70+ (p=0.02, OR= 2.1), and development of rash (p<0.01, OR=3.6), and diarrhea (p=0.03, OR=1.8) were associated with higher response rates. These variables were also associated with longer OS and PFS. Conclusions: Clinical parameters that appear to predict response to EGFR TKI include PS and age. EGFR mechanistic toxicities that develop during therapy are highly associated with benefit and suggest a relationship between drug exposure and outcome. No significant financial relationships to disclose.