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Heinz Zwierzina



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    P3.04 - Immunooncology (Not CME Accredited Session) (ID 970)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.04-01 - Combined Plasma cfDNA Mutations and a Serum Proteomic Signature may Identify Non-Responders to Anti PD-1 Treatment in NSCLC (ID 13166)

      12:00 - 13:30  |  Author(s): Heinz Zwierzina

      • Abstract
      • Slides

      Background

      Predictive scoring systems, for example the status of programmed death-ligand 1 (PD-L1), provide physicians a tool to prescribe immune checkpoint inhibitors for patients diagnosed with non-small cell lung cancer (NSCLC). However, a significant percentage of patients do not respond to these therapies. Additional predictive biomarkers, which further define subpopulations that will benefit from these drugs, are needed.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Serum/plasma samples, clinical and survival data were available for 20 patients with NSCLC that received anti PD-1 therapy either in first (n=1) or second line or later (n=19). Serum/plasma samples were acquired on the day when immunotherapy was administered the first time and at the timepoint of first staging, following initiation of therapy. Plasma samples were analysed for circulating KRAS (G12C, G12D, G12V) and EGFR (E746-A750, L858R, T790M) mutation status by droplet digital PCR (the GeneStrat test). Furthermore, matrix assisted laser desorption/ionization (MALDI) mass spectra were acquired from the matched serum samples using a proteomic test (the VeriStrat test). VeriStrat creates a profile of eight protein features and uses a supervised machine learning algorithm to define outcome subgroups.

      4c3880bb027f159e801041b1021e88e8 Result

      Four patients were found to harbour either EGFR or KRAS mutations or a combination of both in circulation. Two patients displayed a mutation in KRAS G12D and EGFR del19 simultaneously. The other two patients exhibited only a mutation in KRAS (either G12V or G12C). Interestingly, three patients harbouring driver mutations displayed a VeriStrat status of poor at first staging and did not benefit from anti PD-1 therapy. The two patients harbouring both EGFR and KRAS mutations had VeriStrat good labels before start of treatment, which switched to poor results at first staging. Only one patient, displaying a single KRAS mutation and a VeriStrat good status before start of treatment showed a partial response at first staging. Of the 16 patients for whom no circulating mutation was present we found no change in VeriStrat status from before start of treatment to first staging.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Integrated analysis of circulating genomic and proteomic markers for patients that will receive therapy aimed at the inhibition of anti-PD1 and anti-PD-L1 axis may further define patient cohorts that will not respond to immunotherapy.

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