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G. Ostoros



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    P1.10 - Poster Session 1 - Chemotherapy (ID 204)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P1.10-022 - Central European Initiative against Lung Cancer: Results of the Inaugural Workshop (ID 1401)

      09:30 - 09:30  |  Author(s): G. Ostoros

      • Abstract

      Background
      Lung cancer is a major health problem in Central Europe where some of the countries have the world-wide highest incidence rates of this cancer. The CENTRAL EUROPEAN INITIATIVE AGAINST LUNG CANCER aims at decreasing the burden of lung cancer in this region. The Inaugural Workshop of this Initiative was planned in order develop strategies to achieve this goal.

      Methods
      Participation at the Workshop was by invitation and more than 100 lung cancer experts from several Central European Countries and Israel did participate. The participants discussed the current status of lung cancer management and suggested strategies for improvement in the various areas of lung cancer management.

      Results
      The Workshop focused on all aspects of lung cancer. There was agreement that lung cancer is a major health problem in all Central European countries and that improvement in all aspects of lung cancer management must be attempted. Prevention strategies have steadily been improved but remain insufficient in most countries. The potential of screening was recognized but routine implementation of screening was not considered to be feasible in most Central European countries at this time. Access to modern radiological imaging such as PET-CT must be improved in many centers. A future project will assess the accuracy of radiological staging in several hospitals. Molecular diagnosis is increasingly implemented in most countries but patient selection for molecular analyses varies between countries. A major area of discussion was the implementation of standard treatments. Multidisciplinary tumor boards have been established in most centers but participants disagreed on whether all or only selected patients should be presented during tumor board meetings. Concerning stage III NSCLC, great heterogeneity with regard to both staging and treatment has been recognized. A future project plans to assess current management of patients with stage III NSCLC and to define areas for improvement. Access to systemic treatment has improved over the years but timely access to novel and expensive drugs remains challenging in several countries. Strategies to increase the scientific co-operation and education have also been discussed and should increasingly be implemented in the future.

      Conclusion
      The Workshop did outline the current status including challenges in the management of patients with lung cancer in Central Europe. Next projects will assess staging accuracy and detailed treatment of patients with locally advanced NSCLC. Future events such as the 14th Central European Lung Cancer Congress in 2014 and the 17th World Congress on Lung Cancer in 2016 in Vienna should also have a major impact on decreasing the burden of lung cancer in Central European countries.

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    P2.11 - Poster Session 2 - NSCLC Novel Therapies (ID 209)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 2
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      P2.11-018 - EGFR mutations in NSCLC patients in Central Europe: the INSIGHT observational study (ID 1635)

      09:30 - 09:30  |  Author(s): G. Ostoros

      • Abstract

      Background
      Central European countries are among those with the highest incidence rates of lung cancer and most of these cancers are smoking-related. The INSIGHT observational study aimed at assessing prevalence and treatment of patients with EGFR mutations in clinical practice in Central Europe. Here we report on the overall findings of this study.

      Methods
      Patients with NSCLC and tested for EGFR mutations between 15 November 2011 and 31 March 2013 in 14 centers from 6 Central European countries (Austria, Czech Republic, Hungary, Poland, Slovakia, Slovenia) were enrolled. EGFR mutations were determined by sequencing, PCR or other techniques.

      Results
      Here we report data on 1009 NSCLC patients who had been enrolled into the INSIGHT study. The patients had the following characteristics: median age 64 (range 29-93), 62% male, 38% female, 99.9% Caucasians, ECOG performance status 0-1, 2 and 3-4 in 79%, 17% and 4%; 19% never-smokers, 46% former smokers, 35% current smokers; 79% adenocarcinomas, 2% adenosquamous carcinomas, 7% squamous cell carcinomas, 9% NSCLC NOS and 3% others; tumor stages I-II, III and IV in 15.5%, 24% and 60.5% of the patients. EGFR mutations were found in 163 (16%) patients. Patients with mutations had the following characteristics: age median 66 (range 34-89) years, 46% male, 54% female, 47% never-smokers, 38% former smokers, 15% current smokers; performance status was recorded in 153 patients and was 0, 1, 2 and 3 in 30%, 50%, 14% and 6% of the patients. The mutation-positive tumors had the following characteristics: 85% adenocarcinomas, 4% adenosquamous carcinomas, 4% squamous cell carcinomas, 2% NSCLC NOS, and 5% others. Among patients with mutations, exon 18 mutations were seen in 7% of the patients, exon 19 mutations in 50% of the patients including deletions in 39%, exon 20 mutations in 12%, exon 21 mutations in 39% including L858R in 28% of the patients. Detailed data on systemic treatment were available for 122 patients with advanced EGFR mutation-positive NSCLC and most of these patients received EGFR-directed tyrosine kinase inhibitors during the course of their disease.

      Conclusion
      The INSIGHT observational study demonstrated that EGFR mutation testing has been established in the participating centres in Central Europe. The mutation rate of 16% is on the upper limit of the range seen in Western European countries but a potential selection bias for testing of patients with higher likelihood of harboring EGFR mutations cannot be excluded. Systemic treatment in patients with EGFR mutations is similar to treatment patterns observed in other countries. This study was supported by Boehringer Ingelheim Regional Center Vienna.

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      P2.11-022 - Phase IV, single-arm study of first-line gefitinib in Caucasian patients with epidermal growth factor receptor (EGFR) mutation-positive, advanced non-small-cell lung cancer (NSCLC): post-hoc exploratory analyses of EGFR mutations in plasma-derived cfDNA samples (ID 1868)

      09:30 - 09:30  |  Author(s): G. Ostoros

      • Abstract

      Background
      Study NCT01203917 assessed the efficacy and safety/tolerability of the EGFRTKI gefitinib in Caucasians with EGFR mutation-positive NSCLC (previously reported). Here we report post-hoc EGFR mutation analyses of plasma-derived, circulating-free DNA (cfDNA), including efficacy (objective response rate [ORR] and progression-free survival [PFS]) by mutation subtype (Exon 19 deletions; L858R point mutations).

      Methods
      Patients: Caucasians; ≥18 yrs; PS 0-2; histologically confirmed Stage IIIA/B/IV EGFR mutation-positive NSCLC eligible for first-line treatment. Treatment: 250mg gefitinib once-daily until disease progression. Primary endpoint: ORR (investigator assessment); secondary endpoints: disease control rate, PFS, overall survival, and safety/tolerability (previously reported). Mandatory tumor and plasma samples were collected at baseline (all screened patients). Post-hoc exploratory analyses: correlation between clinical characteristics and baseline plasma cfDNA EGFR mutation status; concordance of plasma cfDNA mutation subtype determination (Exon 19 deletions; L858R) with tumor; gefitinib efficacy by plasma cfDNA mutation subtype (Exon 19 deletions; L858R).

      Results
      Of 1060 screened patients with NSCLC, 118 presented with activating, sensitizing EGFR mutations, 106 of whom were enrolled and treated with gefitinib (Full Analysis Set; 71% female; 97% adenocarcinoma; 64% never-smoker). Mutation rate for samples with known mutation status: 14% (118/859) in tumor, 10% (82/784) in plasma. Among 784 patients with baseline plasma samples of known mutation status, histology (adenocarcinoma vs non-adenocarcinoma; odds ratio [OR] 5.54; p=0.0012), smoking status (never- vs ever-smoker; OR 4.39; p<0.0001), and gender (female vs male; OR 2.68; p=0.0004) independently predicted plasma cfDNA mutation status. Concordance in 652 matched tumor and plasma- Exon 19 deletions: 96% (confidence interval [CI]: 95-98); L858R: 98% (CI: 96-99). Using tumor mutation status as reference, EGFR mutation test sensitivity in cfDNA (Exon 19 deletions) was 68% (CI: 56-78), specificity was 100% (CI: 99-100); positive predictive value: 100% (CI: 93-100); negative predictive value: 96% (CI: 94-98); results were similar for L858R, with numerically lower sensitivity (62%; CI 44-78%). ORR for patients with both EGFR mutation-positive tumor and plasma for Exon 19 deletions (n=45): 82% (CI: 69-91); L858R (n=20): 65% (CI: 41-85) (Table). Median PFS for patients with both EGFR mutation-positive tumor and plasma for Exon 19 deletions (25 events): 10.3 months (CI: 8.5-12.4); L858R (11 events): NC. Table

      ORR with gefitinib: baseline tumor vs plasma samples
      Tumor Plasma
      N Responders ORR, % 95% CI N Responders ORR, % 95% CI
      All mutations 106 74 70 61-78 65 50 77 65-86
      Exon 19 deletions 69 50 73 61-82 45 37 82 69-91
      L858R point mutations 33 21 64 47-78 20 13 65 41-85
      Median PFS with gefitinib for baseline tumor vs plasma samples
      Tumor (FAS, N=106) Plasma (N=65)
      Events, N PFS, months 95% CI Events, N PFS, months 95% CI
      All mutations 61 9.7 8.5-11.0 36 10.2 8.5-12.5
      Exon 19 deletions 41 9.6 8.0-11.0 25 10.3 8.5-12.4
      L858R point mutations 19 NC NC 11 NC NC
      NC, not calculated

      Conclusion
      EGFR mutation status assessment of common mutations from plasma-derived cfDNA can be considered when tumor tissue is unavailable. In this context, cfDNA might be used to guide treatment decisions with EGFRTKI therapy, as patients with mutation-positive cfDNA, regardless of mutation subtype, appear to have similar ORR to tumor mutation-positive patients.

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    P3.11 - Poster Session 3 - NSCLC Novel Therapies (ID 211)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P3.11-020 - Epidermal growth factor receptor (EGFR) mutation analyses in tumor and plasma samples from a Phase IV, single-arm study of first-line gefitinib in Caucasian patients with EGFR mutation-positive, advanced non-small-cell lung cancer (NSCLC) (ID 1807)

      09:30 - 09:30  |  Author(s): G. Ostoros

      • Abstract

      Background
      Study NCT01203917 assessed the efficacy, and safety/tolerability of the EGFR tyrosine kinase inhibitor gefitinib in Caucasians with EGFR mutation-positive NSCLC, and compared mutation status in tumor-derived DNA and plasma-derived circulating-free DNA (cfDNA).

      Methods
      Patients: Caucasians; ≥18 yrs; PS 0-2; histologically confirmed Stage IIIA/B/IV EGFR mutation-positive NSCLC eligible for first-line treatment. Treatment: 250mg gefitinib once-daily until disease progression. Primary endpoint: objective response rate (ORR; investigator assessment). Secondary endpoints: disease control rate (DCR; complete/partial response or stable disease ≥6 wks), progression-free survival (PFS), overall survival (OS) and safety/tolerability. Pre-planned exploratory objectives: comparison of EGFR mutation status in tumor versus mandatory, duplicate plasma samples (all screened patients) collected at baseline (plasma1 and 2) and one optional plasma at progression.

      Results
      Of 1060 screened patients with NSCLC, 118 presented with activating, sensitizing EGFR tumor mutations, 106 of whom were enrolled and treated with gefitinib (Full Analysis Set; 71% female; 97% adenocarcinoma; 64% never-smoker). ORR (70%), DCR (90.6%), median PFS (9.7m), and median OS (19.2m) indicated gefitinib efficacy, with rash (45%), and diarrhea (31%) the most common adverse events (AEs; any grade; serious AEs: 19%) (previously reported at EMCTO 2013). Mutation rate for samples with known mutation status: 14% (118/859) in tumor, 10% (82/784) in plasma1. In 201 screened patients, tumor mutation status could not be detected due to technical reasons; however, 12 had a mutation in plasma1. Mutation status concordance in 652 matched tumor and plasma1: 94% (CI: 92-96; mutation subtype/frequencies in Table). Using tumor mutation status as reference, EGFR mutation test sensitivity in cfDNA was 66% (CI: 56-75), specificity was 100% (CI: 99-100); positive predictive value: 99% (CI: 92-100); negative predictive value: 94% (CI: 92-96). Mutation status concordance in 224 duplicate plasma samples: 97% (CI: 94-99) (subtype/frequencies in Table). ORR (post-hoc) for patients with both EGFR mutation-positive tumor and plasma1 or 2 (n=66): 77% (CI: 66-86); ORR for patients with EGFR mutation-positive tumor and EGFR mutation-negative plasma1 or 2 (n=37): 60% (CI: 44-74). Of 12 patients with baseline and progression plasma samples, 4 differences were observed: no mutations were detected at progression in 3 patients in which exon 19 deletions were detected at baseline; one patient with an exon 19 deletion at baseline acquired an additional mutation, T790M (75% concordance; CI: 43-95). Table

      Baseline tumor EGFR mutation subtype results and corresponding plasma 1 results for 652 patients with matched tumor and plasma1 samples
      Plasma1,n TOTAL
      Positive: Exon 19 deletions Positive: L858R Positive: L858R & T790M Negative
      Tumor, n Positive: Exon 19 deletions 48 0 0 23 71
      Positive: L858R 0 21 0 12 33
      Positive: L858R & T790M 0 0 0 1 1
      Negative 0 1 0 546 547
      TOTAL 48 22 0 582 652
      Baseline plasma1 EGFR mutation subtype results and corresponding plasma2 results for 224 patients with duplicate plasma1 and 2 samples
      Plasma2, n TOTAL
      Positive: Exon 19 deletions Positive: L858R Negative
      Plasma1, n Positive: Exon 19 deletions 43 0 4 47
      Positive: L858R 0 20 1 21
      Negative 1 1 154 156
      TOTAL 44 21 159 224

      Conclusion
      First-line gefitinib was effective and well tolerated in Caucasian patients with EGFR mutation-positive NSCLC. EGFR mutation status assessment from plasma-derived cfDNA can be considered when tumor tissue is unavailable.