EGFR Mutation Testing From the Pathologist’s Point of View Ka Fai To, MBChB Chairman and Professor Department of Anatomical and Cellular Pathology The Chinese University of Hong Kong Honorary Chief of Service Department of Anatomical and Cellular Pathology Prince of Wales Hospital Associate Director State Key Laboratory in Oncology in South China

EGFR Mutation Frequency in Different Populations Country EGFR Mutation-Positive Rate Percentage of Patients China 372/741 50.2% Hong Kong 76/161 47.2% India 16/72 22.2% Philippines 34/65 52.3% Taiwan 108/174 62.1% Thailand 63/117 53.8% Vietnam 77/120 64.2% EGFR = epidermal growth factor receptor Yang PC, et al. ASCO 2012. Abstract 1534.

EGFR Mutation Frequency by Sex EGFR Mutation-Positive Rate Percentage of Patients Male 362/822 44.0% Female 384/628 61.1% Yang PC, et al. ASCO 2012. Abstract 1534.

EGFR Mutation Frequency by Smoking Status EGFR Mutation-Positive Rate Percentage of Patients Never smoker 462/761 60.7% Heavy smokers (50 packs/year) NA 31.4% Sex and Smoking Status Male never smoker 104/184 56.5% Female never smoker 358/577 62.0% Male regular smoker 113/301 37.5% Female regular smoker 8/23 34.8% Yang PC, et al. ASCO 2012. Abstract 1534.

EGFR Mutation Frequency by Disease Stage EGFR Mutation-Positive Rate Percentage of Patients IIIB 117/271 43.2% IV 612/1144 53.5% Other 17/35 48.6% Yang PC, et al. ASCO 2012. Abstract 1534.

Local Hong Kong Data: Prince of Wales Hospital, Hong Kong, China Female Male Disease Stage

EGFR Mutation Status Cannot Be Determined by Population Characteristics Ideally, oncologists first seeing their patients with newly diagnosed advanced-stage NSCLC already have the EGFR mutation data to facilitate their choice of an optimal treatment plan for a particular patient. Require reflex EGFR mutation testing NSCLC = non-small cell lung cancer

Rationale for Reflex EGFR Mutation Testing Availability of suitable tumor samples Reflex EGFR mutation testing would help to assess the adequacy of tumor sample at the time of pathological diagnosis After making a request for EGFR mutation testing, time required for: Transportation of sample to EGFR mutation testing molecular laboratory Laboratory turn-around time for the EGFR mutation testing Reflex EGFR mutation testing would shorten the time and would not delay the treatment decision.

Barriers to Reflex EGFR Mutation Testing Recognition of the benefits of reflex EGFR mutation testing Adequacy of tumor samples for EGFR mutation testing Availability of EGFR mutation testing service Reimbursement issues

Multidisciplinary Management Is Crucial Pulmonologists, cardiothoracic surgeon, radiologists, oncologist, and pathologists Right drug to the right patient at the right time

Pathologists: Key Role in Optimized EGFR Mutation Analysis Pathological diagnosis Making a diagnosis of primary NSCLC is not adequate Subtype NSCLC into adenocarcinoma, squamous cell carcinoma, etc. Test all lung cancers with adenocarcinoma component Ensure best possible samples for diagnostic and molecular biomarker studies Assessment of sample adequacy for molecular testing (microdissection to enrich tumor cell content if required) Select the appropriate EGFR mutation testing platform Provide the EGFR mutation testing result in a timely fashion

Only an EGFR mutation test will confirm or exclude the possibility of EGFR mutation.

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