Whats on the Horizon? - PowerPoint PPT Presentation

whats on the horizon n.
Download
Skip this Video
Loading SlideShow in 5 Seconds..
Whats on the Horizon? PowerPoint Presentation
Download Presentation
Whats on the Horizon?

play fullscreen
1 / 62
Whats on the Horizon?
137 Views
Download Presentation
garson
Download Presentation

Whats on the Horizon?

- - - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript

  1. Whats on the Horizon? David Thomson, Lead Pharmacist, Yorkshire Cancer Network.

  2. Overview • YCN Approach • Breast Cancer • Novel Cytotoxics • ErbB Receptor Pathway • Lung Cancer • VEGF/R Pathway • Colorectal Cancer • Biological Combinations • Renal Cell Carcinoma • Sequence and combinations • New agents targeting alternative pathways • “Best of the rest” in other clinical areas

  3. YCN Horizon Scanning • To provide advanced notice to organisations within the YCN of key new and emerging drugs around 1-3 years prior to launch in the UK. • Designed to be informative rather than detailed and definitive. • The reports outline: • What the drug is? • Likely patient population? • Available research evidence? • Prediction of likely use and its potential financial impact in the YCN.

  4. YCN Chemotherapy Management Database

  5. Assumptions • Evidence – this is a summary only. Refer to the clinical data referenced. • Dosing details – indicates how the drug may be used i.e dosing regimen. Predicted length of course is presented as follows: median values are taken from trial data; assumptions are based on trial end-points such as PFS, TTP; if no trial data available an estimate is used. • Cost per patient – assumes full courses and doses are given. Drug prices quoted are the acquisition costs (most recent BNF) of the drug in column 1 only and make the following assumptions: include VAT; wastage where appropriate; av. S.A. 1.75m2; av. wt 75kg. • Incidence – these are estimated figures and are presented as either expected number of patients per 100,000 population or as the total estimated number of patients. 100% uptake assumed unless stated otherwise. • Budget – this assumes a full year effect i.e. that all eligible patients receive their full course of therapy within that financial year. The following assumptions apply: YCN population 2,600,000; HYCCN population 1,100,000.

  6. Horizon Scanning Report

  7. Disclaimer! • The information used in producing these reports changes rapidly and the level of evidence presented and conclusions made about a drug’s potential impact must be treated with caution. • Reports are not intended to be a definitive statement on the safety, efficacy or effectiveness of the drug. • It should also be noted that just as drugs that are included in reports may not be required in the YCN or eventually launched in the UK there may also be drugs not included in reports that are eventually launched in the UK and required within the YCN.

  8. The Challenge

  9. Predicted New Drug Approval Dates

  10. Overview • YCN Approach • Breast Cancer • Novel Cytotoxics • ErbB Receptor Pathway • Lung Cancer • VEGF/R Pathway • Colorectal Cancer • Biological Combinations • Renal Cell Carcinoma • Sequence and combinations • New agents targeting alternative pathways • “Best of the rest” in other clinical areas

  11. Overview • YCN Approach • Breast Cancer • Novel Cytotoxics • ErbB Receptor Pathway • Lung Cancer • VEGF/R Pathway • Colorectal Cancer • Biological Combinations • Renal Cell Carcinoma • Sequence and combinations • New agents targeting alternative pathways • “Best of the rest” in other clinical areas

  12. Novel Paclitaxel Formulations

  13. Epothilone Analogues

  14. Vinflunine • Novel cytotoxic agents – Summary • Good data in breast cancer resistant to taxane therapy. • Combination with targeted therapies as first-line therapy. • Adjuvant therapy.

  15. Overview • YCN Approach • Breast Cancer • Novel Cytotoxics • ErbB Receptor Pathway • ErbB Monoclonal Antibodies • ErbB Tyrosine Kinase Inhibitors • Lung Cancer • VEGF/R Pathway • VEGF Monoclonal Antibodies • VEGFR Tyrosine Kinase Inhibitors • Colorectal Cancer • Combinations • Renal Cell Carcinoma • Sequence and combinations • New agents targeting alternative pathways • “Best of the rest” in other clinical areas

  16. ErbB Receptor Family Zhang H, Berezov A, Wang Q. ErbB receptors: from oncogenes to targeted cancer therapies. J. Clin. Invest. 2007; 117: 2051-2058.

  17. HER2 MoAbs – Pertuzumab

  18. ErbB TKI’s - Lapatinib • Targets HER2 (ErbB2) and EGFR (ErbB1) • Crosses blood brain barrier?

  19. Current Lapatinib Trials

  20. Second Generation ErbB TKI’s • New strategies • Covalent irreversible binding to target • Broadening the affected targets

  21. ErbB Target - Summary • Combinations with/without chemotherapy: • EGFR MoAbs + VEGF MoAbs • EGFR + VEGFR TKI’s • EGFR MoAb + EGFR TKI • Irreversible TKI’s • Adjuvant therapy

  22. Overview • YCN Approach • Breast Cancer • Novel Cytotoxics • ErbB Receptor Pathway • Lung Cancer • VEGF/R Pathway • Colorectal Cancer • Biological Combinations • Renal Cell Carcinoma • Sequence and combinations • New agents targeting alternative pathways • “Best of the rest” in other clinical areas

  23. Lung Cancer

  24. Has chemotherapy in advanced NSCLC done all it can?

  25. Overview • YCN Approach • Breast Cancer • Novel Cytotoxics • ErbB Receptor Pathway • Lung Cancer • VEGF/R Pathway • VEGF Monoclonal Antibodies • VEGFR Tyrosine Kinase Inhibitors • Colorectal Cancer • Biological Combinations • Renal Cell Carcinoma • Sequence and combinations • New agents targeting alternative pathways • “Best of the rest” in other clinical areas

  26. VEGF/R Pathway

  27. Ongoing Bevacizumab Trials

  28. Small-molecule TKI’s VS MoAb’s

  29. VEGFR TKI’s for NSCLC – ASCO 2007

  30. Is potency important?

  31. Or are other factors?

  32. Dual Kinase Inhibition - Vandetinib

  33. VEGF/R Target - Summary • Bevacizumab • High risk patients • Combination therapy (with chemo+/-biologics) • Earlier stage disease • Novel TKI’s • TKI’s versus MoAbs? • Is potency important? • Dual kinase vs single kinase inhibitors?

  34. Overview • YCN Approach • Breast Cancer • Novel Cytotoxics • ErbB Receptor Pathway • Lung Cancer • VEGF/R Pathway • Colorectal Cancer • Combinations • Renal Cell Carcinoma • Sequence and combinations • New agents targeting alternative pathways • “Best of the rest” in other clinical areas

  35. Current Treatments • Irinotecan, oxaliplatin, capecitabine, bevacizumab, cetuximab. • Optimal combinations • Optimal sequences : maintenance vs holidays • Duration of therapy

  36. Bevacizumab vs Cetuximab Combinations

  37. Why target both VEGF and ErbB? • EGFR inhibitors known to exert angiogenic effects by reducing expression of VEGF and other pro-angiogenic factors by tumour cells • EGFR may be induced on tumour epithelium and contribute to tumour angiogenesis • Acquired resistance to EGFR blockade is associated with increased VEGF expression Combinations - Summary Combined VEGF/EGFR inhibition may therefore provide a more potent antiangiogenic effect in addition to direct effects on EGFR+ tumour cells Is maintenance therapy of benefit?

  38. Ongoing Studies

  39. Overview • YCN Approach • Breast Cancer • Novel Cytotoxics • ErbB Receptor Pathway • Lung Cancer • VEGF/R Pathway • Colorectal Cancer • Biological Combinations • Renal Cell Carcinoma • Sequence and combinations • New agents targeting alternative pathways • “Best of the rest” in other clinical areas

  40. mTOR Pathway - Temsirolimus Rini B, Kar S, Kirkpatrick P. Temsirolimus. Nature Reviews Drug Discovery 2007; 6: 599-600

  41. Temsorilumus

  42. Sequence and Combination in mRCC – ASCO 2007

  43. New agents in mRCC – ASCO 2007?