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Matthias Scheffler



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    Lunch & Poster Display session (ID 58)

    • Event: ELCC 2019
    • Type: Poster Display session
    • Track:
    • Presentations: 3
    • Moderators:
    • Coordinates: 4/11/2019, 12:30 - 13:00, Hall 1
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      147P - Impact on KRAS-subtypes and TP53 mutations on the prognostic value of KRAS/KEAP1 comutations in non-small cell lung cancer (NSCLC) (ID 493)

      12:30 - 13:00  |  Presenting Author(s): Matthias Scheffler

      • Abstract
      • Slides

      Background

      Recent studies suggest a devastating impact of KEAP1 mutations on survival in systemically treated advanced NSCLC for both KRAS-comutated and KRAS-wildtype patients. KRAS G12C mutations differ in their co-mutational properties from other KRAS mutations, and TP53 mutations affect the outcome in a subset of NSCLC like ALK-positive NSCLC. We set out this analysis to determine the impact of both KRAS G12C and co-occurring TP53 mutations on the prognostic value of KRAS/KEAP1 comutations.

      a9ded1e5ce5d75814730bb4caaf49419 Methods

      We pooled the data from three different analyses between 2013 and 2018 and looked for patients with stage IV NSCLC for whom survival data was available and who received systemic therapy. The patients had to be diagnosed by a comprehensive next-generation sequencing panel, comprising at least KRAS, KEAP1and TP53 mutations. Median overall survival (mOS) was assessed using Kaplan Meier statistics.

      20c51b5f4e9aeb5334c90ff072e6f928 Results

      We identified 35 patients with KRAS/KEAP1 comutation and available survival data. G12C was detected in 22 patients (62.9%). A co-occurring TP53 mutation could be found in 15 patients (42.9%), and 11 patients (31.4%) presented with both aberrations beside a KEAP1 mutation. 15 patients (42.9%) had neither comutation. The mOS for the whole cohort was 9.8 months (95% CI, 6.3-13.3 months). Neither the presence of a G12C mutation (mOS 9.8 months [5.7-13.4], log rank p = 0.724) nor the presence of a co-occurring TP53 mutation (mOS 9.0 months [5.8-12.2], log rank p = 0.407) had a significant influence on the outcome. For G12C/TP53 beside KEAP1 mutations, there was hardly any difference to the comparison cohort (mOS 9.8 months [5.4-14.2], log rank p = 0.998). Patients without G12C and TP53 had an mOS of 10.4 months (3.6-17.2 months, log rank p = 0.467).

      fd69c5cf902969e6fb71d043085ddee6 Conclusions

      The comutation status of TP53 mutations and/or the presence of the KRAS G12C subtype have no impact on the prognostic value of KRAS/KEAP1-mutated stage IV NSCLC. Further investigations are ongoing to reveal the influence of the mode of systemic therapy in larger cohorts to confirm these findings.

      b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study

      The authors.

      213f68309caaa4ccc14d5f99789640ad Funding

      Has not received any funding.

      682889d0a1d3b50267a69346a750433d Disclosure

      All authors have declared no conflicts of interest.

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      178P - Feasibility of O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET for treatment monitoring of brain metastases in lung cancer patients (ID 561)

      12:30 - 13:00  |  Author(s): Matthias Scheffler

      • Abstract

      Background

      Brain metastases (BMs) occur frequently in patients with advanced lung cancer. So far, intracranial efficacy of systemic lung cancer treatment is nearly unpredictable. Contrast-enhanced magnetic resonance imaging (MRI) is considered gold standard for response assessment but lacks potential to discriminate between malignant or active tumor lesions from benign or postinflammatory signal alterations. O-(2- [18F]fluoroethyl)-L-tyrosine (FET)-positron emission tomography (PET) has shown additional diagnostic value over standard MRI in glioma patients. We set out this analysis to determine the feasibility of FET PET in lung cancer patients.

      a9ded1e5ce5d75814730bb4caaf49419 Methods

      FET with a mean activity of 200 MBq was produced and FET PET performed 20-40 minutes post injectionem at Research Center Juelich (Forschungszentrum Jülich). Patients with cerebral metastasized lung cancer underwent at least one tomography, and tumor volume and activity were assessed by both standard uptake values (SUVs) or tumor-to-brain ratios. A lesion-brain ratio in the standard uptake value (SUV) of more than 2 was considered pathological.

      20c51b5f4e9aeb5334c90ff072e6f928 Results

      From 2015 to 2018, 48 patients received at least one FET PET, whereof 11 patients (22.9%) underwent two scans and one patient three serial FET PETs. All scans could be analyzed for the assessment of tumor activity. The patients did not suffer of adverse events related to the tracer or the procedure. In most cases, FET PET was performed to discriminate between scar tissue and new tumor activity in singular metastases treated stereotactically. In a smaller number of patients, FET PET was used to assess treatment response in systematically treated patients.

      fd69c5cf902969e6fb71d043085ddee6 Conclusions

      FET PET is feasible in patients with brain metastases of lung cancer and might provide additional information to MRI for treatment decisions in these patients. Validation of the results and the reproducibility is ongoing.

      b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study

      The authors.

      213f68309caaa4ccc14d5f99789640ad Funding

      Has not received any funding.

      682889d0a1d3b50267a69346a750433d Disclosure

      All authors have declared no conflicts of interest.

      cffcb1a185b2d7d5c44e9dc785b6bb25

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      184TiP - FIND: A phase II study to evaluate the efficacy of erdafitinib in FGFR-altered squamous NSCLC (ID 571)

      12:30 - 13:00  |  Author(s): Matthias Scheffler

      • Abstract

      Background

      Genomic FGFR alterations and their oncogenic driver potential are frequently observed in various cancers. Initial clinical trials with selective FGFR inhibitors showed moderate responses in FGFR amplified squamous NSCLC (sqNSCLC) patients. However, in FGFR mutated or translocated tumor types a response rate of above 30% was observed. Preclinical cell line and patient-derived sqNSCLC xenograft models with FGFR mutations or translocations indicate strong oncogenic activity and potential sensitivity to FGFR inhibitors. Approximately 3% of all sqNSCLC patients harbor somatic alterations within FGFR genes. However, only some of these mutations are shown to be oncogenic drivers in vitro and in vivo experiments or first in man trials.

      a9ded1e5ce5d75814730bb4caaf49419 Trial design

      Screening for FGFR mutations/translocations will be performed within the national Network of Genomic Medicine in 15 screening centers in Germany. SqNSCLC patients with activating FGFR genetic alterations will be treated in 11 clinical centers in Germany with the selective FGFR1-4 kinase inhibitor erdafitinib. Archival samples, fresh frozen tumor samples and blood for circulating tumor DNA will be collected before treatment and at time of progression. Patients will be treated until disease progression or unacceptable toxicity. The primary objective of the trial is to analyze the efficacy of erdafitinib in sqNSCLC patients with FGFR genetic driver alterations. Patients will be recruited into 3 cohorts: Cohort 1: high confidence activating FGFR translocations (max. 15 patients); Cohort 2: high confidence activating FGFR mutations (max. 15 patients); Cohort 3: low confidence activating FGFR alteration (ca. 20 patients). The study has been currently submitted by authorities and is currently targeted to start recruitment in Q1/2019.

      d9b324a48b043b3d87bc9b3fe620f260 Clinical trial identification

      EudraCT: 2018-000399-13.

      7a6a3ffa2dadc03a6151ee2c4d6fa383 Legal entity responsible for the study

      University of Cologne.

      213f68309caaa4ccc14d5f99789640ad Funding

      Janssen.

      682889d0a1d3b50267a69346a750433d Disclosure

      L. Nogova: Honoraria, advisory boards, travel fees: Boehringer Ingelheim, BMS, Celgene, Roche, Pfizer, Janssen, Novartis; Grants to institution: Pfizer, Novartis, BMS, Janssen. A. Hillmer: Honoraria, advisory board: MSD. S. Merkelbach-Bruse: Honoraria, advisory boards: Novartis, Roche. A. Pinto, C. Woempner: Grants to institution: BMS, Pfizer, Novartis, Janssen. R. Riedel: Honoraria, advisory boards: Boehringer Ingelheim, Novartis; Travel fee: Boehringer Ingelheim, Novartis, Lilly; Grants to institution: BMS, Pfizer, Novartis, Janssen. M. Scheffler: Honoraria, advisory boards: Boehringer Ingelheim; Grants to institution: Pfizer, BMS, Novartis, Janssen. S. Michels: Honoraria, Advisory boards: Novartis; Grants to institution: Pfizer, BMS, Novartis, Janssen. P. De Porre, A. Santiago-Walker: Employee: Janssen; Owning stock: J&J. R.N. Fischer: Honoraria: Bristol-Myers Squibb, MSD, Roche, Boehringer Ingelheim, Novartis, AstraZeneca; Grants to institution: Pfizer, BMS, Novartis, Janssen. D.S. Abdulla: Honoraria, advisory boards: Boehringer Ingelheim, Roche, AbbVie; Grants to institution: Pfizer, Novartis, BMS, Janssen. J. Wolf: Advisory boards, Honoraria, travel fees: AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Chugai, Ignyta, Lilly, MSD, Novartis, Pfizer, Roche; Grants to institution: MSD, BMS, Pfizer, Novartis, Janssen. All other authors have declared no conflicts of interest.

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