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S. Tjulandin



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    P1.06 - Poster Session 1 - Prognostic and Predictive Biomarkers (ID 161)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P1.06-022 - Investigating the utility of plasma derived circulating free DNA for the detection of epidermal growth factor receptor (EGFR) mutations in European and Japanese patients with advanced non-small-cell lung cancer (NSCLC): ASSESS study design (ID 1801)

      09:30 - 16:30  |  Author(s): S. Tjulandin

      • Abstract

      Background
      In patients with NSCLC, accurate and accessible EGFR mutation testing is important for guiding treatment decisions. Current procedures involve the testing of biopsy or cytology samples, which are not always available from all patients. However, plasma of patients with advanced NSCLC contains circulating-free tumor-derived DNA (cfDNA) that is suitable for mutational analysis. The large, multi-center, non-interventional, non-comparative ASSESS diagnostic study (NCT01785888) will evaluate the utility of plasma-based testing compared with tissue or cytology-based testing as a less invasive methodology by which to assess EGFR mutation status in patients with NSCLC.

      Methods
      A total of 1300 patients (age ≥18 years in Europe; ≥20 years in Japan) with newly diagnosed locally advanced/metastatic (Stage IIIA/B/IV) chemotherapy-naïve NSCLC who are not eligible for curative treatment, or patients with recurrent disease after surgical resection with/without adjuvant chemotherapy, will be screened for EGFR mutation status in tumor and plasma across Japan and 7 European countries over 18 months. To allow determination of sensitivity between tumor and plasma-based EGFR screening (95% confidence interval [CI] 40-60%, assuming 50% sensitivity), 100 patients each with mutation-positive NSCLC in Europe (EGFR mutation frequency: ~10%) and Japan (EGFR mutation frequency: ~30%) will be required; 1000 and 300 patients will therefore be enrolled from Europe and Japan, respectively. Provision of tumor (biopsy/cytology/other tumor cell sample) and plasma samples for EGFR mutation testing will be mandatory. Precise clinical phenotyping will be performed, and clinical information about first line (all patients) and second line (patients with mutation-positive NSCLC) therapy decisions will be recorded. EGFR testing will be performed according to local practices, with Exon 19 deletions and L858R point mutations assessed as a minimum. The primary objective is determination of concordance between EGFR mutation status obtained via tissue/cytology and plasma-based testing (concordance rate, sensitivity, specificity, positive and negative predictive values, and exact 2-sided 95% CIs). Secondary objectives: determination of EGFR mutation frequency (including mutation subtypes) in patients with adenocarcinoma/non-adenocarcinoma NSCLC; description of first-line (all patients) and second-line (all available patients) therapy following mutation testing; characterization of current EGFR testing practices; correlation between EGFR mutation status identified in tumor/plasma samples and demographic/disease status data. Pre-planned exploratory objective: investigation of exploratory biomarkers which may help to define molecular features of NSCLC (prevalence, co-occurrence, correlation with demographic data) using optional, additional tumor (biopsy/cytology/other) samples. The secondary analyses from the study will help define the current status of EGFR mutation testing procedures across Japan and Europe, and provide further information regarding mutation frequency across patient subgroups, and the relationship between EGFR mutation status and therapy decisions.

      Results
      Not applicable.

      Conclusion
      Not applicable.

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    P3.06 - Poster Session 3 - Prognostic and Predictive Biomarkers (ID 178)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P3.06-053 - A diagnostic study to determine the prevalence of epidermal growth factor receptor (EGFR) mutations in Asian and Russian patients with non-small cell lung cancer (NSCLC) of adenocarcinoma and non-adenocarcinoma histology: IGNITE study design (ID 1610)

      09:30 - 16:30  |  Author(s): S. Tjulandin

      • Abstract

      Background
      EGFR mutation status is widely accepted as an important biomarker in NSCLC. To assess the current status of EGFR mutation testing, including testing procedures, sample types, mutation prevalence across demographic/histological subgroups (adenocarcinoma and non-adenocarcinoma histologies), and impact of EGFR mutations on personalized therapy choice, a large, multinational, diagnostic, non-comparative, interventional study (NCT01788163; IGNITE) of EGFR mutation status in patients with locally advanced/metastatic NSCLC of adenocarcinoma and non-adenocarcinoma histology will be conducted across centers in the Asia Pacific region and Russia.

      Methods
      Approximately 3500 patients (age ≥18 years) with chemotherapy naïve, Stage IIIA/B/IV NSCLC (newly diagnosed or recurrent disease after surgical resection) that is not suitable for curative treatment will be recruited over ~18 months from Asia Pacific (including 25 centers in China) and Russia. To give similar precision for the estimation of EGFR mutation frequency in the key non-adenocarcinoma subgroup in Asia Pacific and Russia, 2500 patients from Asia Pacific (assumptions: 20% patients non-adenocarcinoma histology, with 10% EGFR mutation frequency [one-fifth of the 50% prevalence in adenocarcinoma]; precision ±3%) and 1000 patients from Russia (assumptions: 20% patients non-adenocarcinoma histology, with 4% EGFR mutation frequency [one-fifth of the 20% prevalence in adenocarcinoma]; precision ±4%) need to be screened. Provision of diagnostic tumor samples for testing will be mandatory for all patients; additionally, plasma samples, which contain circulating-free tumor derived DNA (cfDNA), will be collected for EGFR mutation testing of plasma from a subset of 2500 patients in Russia, China, Taiwan and Korea. EGFR testing will be performed according to local practices, with Exon 19 deletions and L858R point mutations assessed as a minimum. The first-line (all patients) and second-line (patients with mutation-positive NSCLC; estimated 50% will progress to second-line treatment by study cutoff) therapy choices will be recorded. The primary objective is to determine EGFR mutation (and subtype) frequency in patients with adenocarcinoma and non-adenocarcinoma NSCLC (overall and by country/region). Secondary objectives are: to describe first-line therapy following EGFR mutation testing and second-line therapy following discontinuation of first-line treatment in patients with EGFR mutation-positive NSCLC confirmed by tissue/cytology; to determine concordance between EGFR mutation status determined using tissue/cytology versus plasma; to summarize current EGFR testing practices (methods, sample types, mutation detection rate, turnaround time, and reasons for not performing testing); to determine correlations between EGFR mutation status (derived from tumor or plasma) and demographic data and disease status. The secondary analyses in this study will provide information on current testing and therapeutic practices in advanced NSCLC across the Asia Pacific region and Russia, as well as an assessment of the utility of cfDNA as a less invasive methodology for the assessment of EGFR mutation status in patients with NSCLC.

      Results
      Not applicable.

      Conclusion
      Not applicable.

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    P3.21 - Poster Session 3 - Diagnosis and Staging (ID 171)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Prevention & Epidemiology
    • Presentations: 1
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      P3.21-002 - Lung-EPICLIN: analysis of <em>EGFR</em> mutations and associated clinico-pathological parameters in patients with NSCLC in Russian Federation (ID 1409)

      09:30 - 16:30  |  Author(s): S. Tjulandin

      • Abstract

      Background
      Lung cancer is a major cause of mortality in Russia: 51,364 deaths in 2008, 18.0% of all cancer-related deaths (GLOBOCAN). Mutations in the EGFR gene are known to predict for sensitivity to EGFR tyrosine kinase inhibitors in patients with advanced non-small-cell lung cancer (NSCLC). Clinico-pathological characteristics associated with a higher prevalence of EGFR mutations are: adenocarcinoma histology, East Asian origin, non-smoking history, and female gender. This study aimed to document the characteristics, clinical management and outcomes of Russian patients with NSCLC, and to investigate associations between EGFR mutations and clinico-pathological parameters.

      Methods
      A non-interventional, prospective cohort study (ClinTrials ID: NCT01069835) carried out in a representative selection of hospitals in order to assess lung cancer management in countries throughout European and Asian parts of Russia. Patients with confirmed NSCLC attending participating centres for the first time between 1 February 2010 and 31 March 2011 were enrolled and followed-up according to routine practice for a minimum of 12 months or until death.

      Results
      A total of 838 patients were enrolled at 33 sites across the Russian Federation. Baseline characteristics were: mean age, 58.7 (SD ±8.5) years; male, 78.4%; European, 98.0%; Russian, 79.6%; Tatar, 3.8%; Ukrainian, 3.1%; Byelorussian, 1.3%; current smokers, 49.4%; never-smokers, 26.5%; ECOG performance status (PS) 1, 65.6%; disease stage IV, 25.4%; stage III, 37.8%; stage I/II, 36.7%. Metastases were found in 38.1% of patients; the most common metastatic sites included: respiratory system, 70.2%; pleura, 17.2%; bone, 11.9%; liver, 10.3%. EGFR mutations were detected in 85/838 (10.1%) patients (84/821 [10.2%] European patients and 1/15 [6.7%] Asian patients), who were mostly women, 69.4%; <70 years old, 85.9%; never smokers, 71.8%; PS 1, 59.3%; adenocarcinoma, 58.8%. EGFR mutation rates by histological type were: squamous-cell carcinoma (SCC), 18/455 (4.0%); adenocarcinoma, 50/260 (19.2%); adenocarcinoma bronchioloalveolar, 11/54 (20.4%); large-cell carcinoma, 2/24 (8.3%); adenosquamous carcinoma, 2/19 (10.5%); other histology, 2/26 (7.7%). Logistic regression analysis of EGFR mutations; statistically significant odds ratios: male vs female, 0.086 (p<0.0001); any smoking history vs no smoking history, 0.110 (p<0.0001); non-SCC vs SCC, 5.365 (p<0.0001); increase in age (10 years), 1.391 (p=0.0227). Platinum-containing doublets were the most commonly used chemotherapy at first (83.5%) and second line (51.0%). In patients who received first- and second-line chemotherapy, objective response rate, disease progression rate and median progression-free survival (PFS) were, respectively, 16.1% and 3.6%, 63.8% and 76.8%, 35.0 weeks and 19.4 weeks. Median PFS (weeks) after first-line chemotherapy by histology and EGFR mutation status was: SCC, 36.3; non-SCC, 34.0; EGFR mutation positive, 36.9; EGFR mutation negative, 34.3.

      Conclusion
      In this cohort, the proportion of patients with EGFR mutation-positive NSCLC was similar to other studies of NSCLC in Caucasian populations. EGFR mutation status was significantly associated with female gender and non-smoking history, in-line with previous studies of Asian and Caucasian patients with advanced NSCLC. This study contributes to a better understanding of prognostic and predictive factors of NSCLC, which will enable optimal treatment selection in future clinical practice.