Targeting the EGFR: Iressa

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11 Apr 2012
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The EGF Receptor
RTK family of cell surface receptors
Includes epidermal growth factor receptor (EGFR/Erb1/Her1) and its relatives
Receptors of EGFR subgroup essential for embryonic development and adult tissue
homeostasis in vertebrates and invertebrates.
Abnormal activation associated with a variety of cancers.
EGFR overexpression in several human tumors.
Prognostic significance of EGFR overexpression in selected cancers: Poor prognosis, low
survival, high risk of metastases
EGFR pathways
Rasproliferation
PI3KAkt cell cycle progression or survival
Non-small-cell lung cancer (NSCLC)
Leading cause of cancer-related mortality
Current therapies
oMinor gaines
oCombine chemo/surgery/radiotherapy
o15% 5 year survival rate
EGFR expressed in most NSCLCs pathophysiological implication as a biomaker
Gefitinib – Iressa
Small molecule TKI of EGFR for treatment of NSCLC
Trials in NSCLC
Gefitinib
oIDEAL-1 Trial
Treat advanced NSCLC with prior chemotherapy prescription
Not a great response rate
Gefitinib + Chemo
oNo difference in survival or time to progression
Gefinitib
oISEL Trial
No difference, but subgroup analysis shoed survival benfit in never-
smokers and Asians – significant difference
Only a small proportion of patients with NSCLC shows dramatic responses to
Iressa
Factors that favor Gefitinib sensitivity
oWoman
oNon-smoker
oJapanese
oAdenocarcinoma
Charactersistcs of patients with NSCLC that respond to Gefitinib:
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