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

1a Systematic Review (with homogeneity*) of RCTs

1b Individual RCT (with narrow Confidence Interval‡)

1c 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.

2a SR (with homogeneity*) of cohort studies

2b Individual cohort study (including low quality RCT; e.g., <80% follow-up)

2c "Outcomes" Research; Ecological studies

3a SR (with homogeneity*) of case-control studies

3b Individual Case-Control Study

4 Case-series (and poor quality cohort and case-control studies§§)

5 Expert 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?