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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 inMetastatic 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 • Cetuximab in combination with CAPOX/FOLFOX - MRC COIN Trial • Updated cetuximab 1st line data • CRYSTAL - updated • OPUS – updated www.OncologyEducation.ca
What did we know before ECCO 2009? www.OncologyEducation.ca
What did we find at ECCO2009? FIRST LINE www.OncologyEducation.ca
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
Gr 3/4 TOXICITY www.OncologyEducation.ca
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
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
UPDATED CRYSTAL RESULTS www.OncologyEducation.ca
UPDATED OPUS RESULTS www.OncologyEducation.ca
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
RESULTS www.OncologyEducation.ca
TOXICITY www.OncologyEducation.ca
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
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
What did we find out at ECCO 2009?SECOND LINE www.OncologyEducation.ca
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
RESULTS www.OncologyEducation.ca
Gr 3/4 TOXICITY www.OncologyEducation.ca
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
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
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