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ECCO 2009 GI Update: Focus on EGFR Inhibitors in Metastatic Colorectal CA (mCRC)

ECCO 2009 GI Update: Focus on EGFR Inhibitors in Metastatic Colorectal CA (mCRC). Scott Berry Sunnybrook Odette Cancer Centree. Overview. EGFR Inhibitors in mCRC NEW DATA: Pmab in combination with chemo data 1st Line with FOLFOX 2nd Line with FOLFIRI

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ECCO 2009 GI Update: Focus on EGFR Inhibitors in Metastatic Colorectal CA (mCRC)

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  1. ECCO 2009 GI Update:Focus on EGFR Inhibitors inMetastatic Colorectal CA (mCRC) Scott Berry Sunnybrook Odette Cancer Centree

  2. Overview • EGFR Inhibitors in mCRC • NEW DATA: • Pmab in combination with chemo data • 1st Line with FOLFOX • 2nd Line with FOLFIRI • Cetuximab in combination with CAPOX/FOLFOX - MRC COIN Trial • Updated cetuximab 1st line data • CRYSTAL - updated • OPUS – updated www.OncologyEducation.ca

  3. What did we know before ECCO 2009? www.OncologyEducation.ca

  4. www.OncologyEducation.ca

  5. What did we find at ECCO2009? FIRST LINE www.OncologyEducation.ca

  6. R FOLFOX4 + Pmab 6 mg/kg q 2 wks FOLFOX4 “PRIME” Study Design N= 656 KRAS WT (1183 total - 92% evaluated for KRAS) 1o Outcome: PFS mCRC No prior oxali > 6 mos after adj 5FU ECOG 0-2 www.OncologyEducation.ca

  7. RESULTS

  8. Gr 3/4 TOXICITY www.OncologyEducation.ca

  9. FOLFIRI N=609 FOLFIRI + Cetuximab N=608 RANDOMI ZE CRYSTAL Trial Updated 10 Endpoint= PFS N=1217 EGFR expression via IHC * Cetuximab 400 mg/m2 IV week 1 then 250 mg/m2 IV weekly 1:1 www.OncologyEducation.ca

  10. FOLFOX N=168 FOLFOX + Cetuximab N=170 RANDOMI ZE OPUS: Rand Phase IIUpdated N=338 EGFR+ Metasatic CRC * Cetuximab 400 mg/m2 IV week 1 then 250 mg/m2 IV weekly 1:1 www.OncologyEducation.ca

  11. www.OncologyEducation.ca

  12. UPDATED CRYSTAL RESULTS www.OncologyEducation.ca

  13. UPDATED OPUS RESULTS www.OncologyEducation.ca

  14. R CAPOX/ FOLFOX CAPOX/ FOLFOX + CETUXIMAB MRC COIN Study Design N= 729 KRAS WT (80 % analyzed, 56% WT) 1o Outcome: OS 66% RECEIVED CAPOX First Line mCRC PS0-2 www.OncologyEducation.ca

  15. RESULTS www.OncologyEducation.ca

  16. TOXICITY www.OncologyEducation.ca

  17. STUDY COMMENTARY • Capecitabine Arm - Analyses not complete but: • Had much higher rates of non-haem toxicity leading to dose reductions and trial amendment - reduction of dose form 2000 mg/m2 to 1700 mg/m2 (Adams, Br J Cancer, 2009) • Hope to have updated analysis at ASCO GI 2010 further examining the issue of efficacy and toxicity of capecitabine cetuximab combination and impact on overall trial results www.OncologyEducation.ca

  18. STUDY COMMENTARY • Median survivals in both study arms lower than other contemporary first line chemo /biologic trials • ? patient population • 9% > 75 • 8% ECOG 2 • ? access to subsequent line tx options www.OncologyEducation.ca

  19. What did we find out at ECCO 2009?SECOND LINE www.OncologyEducation.ca

  20. R FOLFIRI + Pmab 6 mg/kg q 2 wks FOLFIRI Study Design N= 597 KRAS WT (1186 total - 92% evaluated for KRAS) 1o Outcome: PFS and OS mCRC Progression < 6 mos after 1 prior Therapy No prior Iri ECOG 0-2 www.OncologyEducation.ca

  21. RESULTS www.OncologyEducation.ca

  22. Gr 3/4 TOXICITY www.OncologyEducation.ca

  23. Summing Up:What do we know after ECCO 2009?

  24. www.OncologyEducation.ca

  25. www.OncologyEducation.ca

  26. Bottom Line for Canadian Medical Oncologists (1) • EGFR Inhibitors in mCRC - Survival benefit now demonstrated: • in 3rd line as monotherapy • with FOLFIRI + Cetux 1st line • FOLFIRI + Cetux emerges as credible 1st line option for KRAS WT patients • ...but not a funded option in Canada at this time • NCIC CRC.5 will address issue of which chemo + biolologic combination is superior first line • Chemo + Bevacizumab vs Chemo + Cetuximab • Double biologic arm dropped by intergroup www.OncologyEducation.ca

  27. FOLFOX or FOLFIRI, bevacizumab and cetuximab FOLFOX or FOLFIRI, and cetuximab FOLFOX or FOLFIRI, and bevacizumab Previously untreated patients with mCRC CALGB 80405 / CRC5 NCIC Chair: S Berry R X Primary Endpoint: Overall Survival www.OncologyEducation.ca

  28. Bottom Line for Canadian Medical Oncologists (2) • EGFR Inhibitors in mCRC - PFS benefit seen with • FOLFOX + Pmab first line • FOLFIRI + Pmab second line • Further analyses of Pmab combos awaited • MRC COIN Trial • ? choice of chemo NB : preliminary signal re CAPOX + cetuximab - further information/analyses of efficacy and safety of COIN trial needed - hopefully available at ASCO GI 2010 www.OncologyEducation.ca

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