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Naoko Sueoka-Aragane



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    P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.01-49 - irAE, Possible Predictive Markers for Immune Checkpoint Inhibitors (ID 12709)

      16:45 - 18:00  |  Author(s): Naoko Sueoka-Aragane

      • Abstract
      • Slides

      Background

      Although an immune-related adverse event (irAE) in immune checkpoint inhibitors (ICIs) is a major cause of discontinuation of ICIs, few reports have examined detailed clinical background in clinical practice.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Sixty-one patients with non-small cell lung cancer who underwent treatment with ICIs (nivolumab or pembrolizumab) at the Saga University Medical School Hospital from December 2015 to January 2018 were included. Clinical background, therapeutic effect, and progression free survival (PFS) were retrospectively examined between AE discontinuation group (AEg) and progressive disease (PD) discontinuation group (PDg).

      4c3880bb027f159e801041b1021e88e8 Result

      Of the 41 patients receiving nivolumab, nine cases (22.5%) were discontinued due to AE and 22 cases (55.0%) were PD. Of 21 patients receiving pembrolizumab, nine cases (42.9%) were discontinued due to AE and 8 cases (38.1%) were PD. There was no significant difference between nivolumab and pembrolizumab in the discontinuation rate due to AE (p=0.14). When comparing the clinical background between the AEg and the PDg, the response rate was 50.0% in the AEg and 6.7% in the PDg, which was significantly higher in the AEg (p=0.001). The median PFS was significantly longer in the AEg, 301 days (95% CI: 193-336) in the AEg and 60 days (95% CI: 74-178) in the PDg (Log-Rank, p=0.009). Among irAE, the incidence of interstitial lung disease (ILD) was 3/49 (6.1%) in cases without interstitial pneumonia (IP) or radiation pneumonitis as the underlying diseases, whereas it was significantly higher at 6/12 (50.0%) in cases with those underlying diseases (p=0.001). Among nine patients who developed ILD, grade3 or more was 2 cases, of which 1 case was grade5.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Discontinuation due to AE during treatment of ICIs may be a predictive marker of good response to ICIs and favorable outcome since anti-cancer effect continued even after discontinuation. However, the presence of IP or radiation pneumonitis as the underlying disease is a risk factor for the onset of ILD, so it is necessary to carefully consider the indication for treatment of ICIs.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P3.13 - Targeted Therapy (Not CME Accredited Session) (ID 979)

    • 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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      P3.13-18 - Mechanisms of Acquired Resistance to Afatinib Clarified with Liquid Biopsy (ID 11925)

      12:00 - 13:30  |  Author(s): Naoko Sueoka-Aragane

      • Abstract
      • Slides

      Background

      While the elucidation of the mechanisms of acquired resistance to 1st and 3rd generation EGFR-TKI progresses, there have been few clinical investigations into the mechanisms of acquired resistance to 2nd generation EGFR-TKI, afatinib.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We analyzed 20 patients with advanced lung adenocarcinoma who acquired resistance to afatinib including EGFR-TKI re-challenge. We examined EGFR T790M, C797S, BRAF V600E, MET amplification by MBP-QP method and droplet digital PCR using ctDNA and re-biopsy samples at pre and post afatinib treatment.

      4c3880bb027f159e801041b1021e88e8 Result

      Just before afatinib treatment, 15 patients were T790M negative, and 5 were positive with ctDNA. Among T790M negative patients, 40.0% (6/15) turned to positive at PD to afatinib. T790M positive patients showed synchronous change of T790M allele frequency with treatment efficacy of afatinib. C797S was not detected just before afatinib treatment, and it appeared in 3 patients with very low level of allele frequency. Two of 3 patients were both C797S and T790M positive, who achieved PR to osimertinib. However, PFS with these patients was a trend shorter than T790M only. BRAF V600E was detected in one patient at PD to afatinib. MET amplification was never detected in this study.

      8eea62084ca7e541d918e823422bd82e Conclusion

      T790M was related with acquired resistance to afatinib like 1st generation EGFR-TKI, but the frequency is relatively lower. The influence of C797S for resistance to afatinib would be less than T790M, but existence of C797S possibly causes shorter PFS of osimertinib.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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