Anti-EGFR treatment: Antibodies What has been the experience with Anti-EGFR antibody therapy in the treatment of squamous cell carcinoma of the head and neck? –Using erbitux (C225, cetuximab)? –Using other antibodies? What are the relative merits/shortcomings of C225 and other antibodies?

Anti-EGFR treatment: Antibodies What settings have these been studied in? What level of evidence exists for each? –Single agent Refractory disease –Combination with chemotherapy Refractory disease Induction therapy Adjuvant therapy - Combination with radiation therapy (will be discussed in a separate session devoted to this topic)

Oxford Centre for Evidence-based Medicine Levels of Evidence (May 2001) Level Therapy/Prevention, Aetiology/Harm 1aSystematic Review (with homogeneity*) of RCTshomogeneity* 1bIndividual RCT (with narrow Confidence Interval‡)Confidence Interval‡ 1cAll or none§All or none§ Met when all patients died before the Rx became available, but some now survive on it; or when some patients died before the Rx became available, but none now die on it. 2aSR (with homogeneity*) of cohort studieshomogeneity* 2bIndividual cohort study (including low quality RCT; e.g., <80% follow-up) 2c"Outcomes" Research; Ecological studies 3aSR (with homogeneity*) of case-control studieshomogeneity* 3bIndividual Case-Control Study 4Case-series (and poor quality cohort and case-control studies§§)poor quality cohort and case-control studies§§ 5Expert opinion without explicit critical appraisal, or based on physiology, bench research or "first principles"

Anti-EGFR treatment: Antibodies Are there any short or long term toxicities unique to the use of antibodies that target the EGF-R?

Anti-EGFR treatment: Antibodies What are the major mechanisms of action of anti-EGFR monoclonal antibodies that make them distinct from small molecule tyrosine kinase inhibitors?

Anti-EGFR treatment: Antibodies What are the major mechanisms of resistance to treatment with anti- EGFR monoclonal antibodies?

Anti-EGFR treatment: Antibodies Are there any molecular predictors (biomarkers) for sensitivity or resistance to treament with anti- EGFR monoclonal antibodies?

Anti-EGFR treatment: Antibodies Is skin rash a predictor for sensitivity or resistance to treament with anti- EGFR monoclonal antibodies?

Anti-EGFR treatment: Antibodies What is the experience with anti EGF-R antibodies in the treatment of tumors of the head and neck region other than Squamous Cell Carcinoma?

Anti-EGFR treatment: Small molecule tyrosine kinase inhibitors (TKIs) What has been the experience with Anti-EGFR TKIs in the treatment of squamous cell carcinoma of the head and neck? –Using gefitinib (Iressa)? –Using other inhibitors (erlotinib)? What are the relative merits/shortcomings of gefitinib and other small molecules?

Anti-EGFR treatment: TKIs What settings have these been studied in? What level of evidence exists for each? –Single agent Refractory disease –Combination with chemotherapy Refractory disease Induction therapy Adjuvant therapy - Combination with radiation therapy (will be discussed in a separate session devoted to this topic)

Anti-EGFR treatment: TKIs Are there any short or long term toxicities unique to the use of TKIs that target the EGF-R?

Anti-EGFR treatment: TKIs What are the major mechanisms of resistance to treatment with anti- EGFR TKIs?

Anti-EGFR treatment: TKIs Are there any molecular predictors (biomarkers) for sensitivity or resistance to treament with anti- EGFR TKIs?

Anti-EGFR treatment: TKIs What is the experience with anti EGF-R TKIs in the treatment of tumors of the head and neck region other than Squamous Cell Carcinoma?

Anti-EGFR treatment: Transcription Inhibitors What has been the experience with Anti-EGFR transcriptional inhibitors for therapy in the treatment of squamous cell carcinoma of the head and neck or other tumor types?