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Anti-EGFR treatment: Antibodies

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?.

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Anti-EGFR treatment: Antibodies

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  1. 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?

  2. 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)

  3. 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" Oxford Centre for Evidence-based Medicine Levels of Evidence (May 2001)

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

  5. 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?

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

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

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

  9. 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?

  10. 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?

  11. 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)

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

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

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

  15. 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?

  16. 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?

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