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Zhihuang Hu



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    JCSE01 - Perspectives for Lung Cancer Early Detection (ID 779)

    • Event: WCLC 2018
    • Type: Joint IASLC/CSCO/CAALC Session
    • Track: Screening and Early Detection
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/23/2018, 07:30 - 11:15, Room 202 BD
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      JCSE01.11 - Dynamic ctDNA Monitoring Revealed Novel Resistance Mechanisms and Response Predictors of Osimertinib Treatment in East Asian NSCLC Patients (Now Available) (ID 14716)

      10:35 - 10:45  |  Author(s): Zhihuang Hu

      • Abstract
      • Presentation
      • Slides

      Background

      Advanced NSCLC patients, harboring EGFR T790M, exhibit marked diversity in tumor behavior and response to AZD9291, yet a discriminable molecular profile remains elusive. In addition, although EGFRC797S was involved in 30% of AZD9291 resistance cases in Western patients, mechanisms for the rest patients remain unclear, especially for the East Asian population. We utilized circulating tumor DNA (ctDNA) profiling to conduct dynamic monitoring in patients undergoing AZD9291, thus characterizing mutational heterogeneity and genomic evolution.

      Longitudinal plasma samples were collected before, during and post of the AZD9291 treatment in Chinese NSCLC patients with acquired T790M mutation. A ctDNA panel, spanning 160KB of human genome, was used to perform capture-based targeted sequencing that comprises critical exons and introns of 168 genes. The EGFR mutation abundance and dynamic changes of allele fraction (AF) were analyzed with progression-free survival (PFS) after AZD9291 treatment.

      A total of 61 samples were collected longitudinally from 14 patients, of which 9 have experienced progressive disease (PD). Six patients exhibited a rebound of ctDNA prior to radiographic PD, suggesting the potential of ctDNA in early detection of PD. Several acquired mutations were detected with the AZD9291 resistance, including newly identified EGFR G796S, L792H/F/R/V, V802F, V843I mutations, expect for the previously reported RB1 and EGFR C797S, L718Q mutations. Patients with a higher ratio of T790M and EGFRactivating mutation at baseline had a significantly longer PFS (9.6m vs 4.5m, p=0.008). A lower ratio of EGFRactivating mutation AF compared to baseline at first follow-up was significantly correlated with a longer PFS (8.5m vs 5.0m, p=0.027). Furthermore, patients harboring other known driver mutations in addition to T790M at baseline had an inferior PFS (4.9m vs 7.8m, P=0.039).

      Several novel resistance mechanisms were identified by ctDNA monitoring in the East Asian patients treated with AZD9291. Relative AF of T790M, changes of AF after treatment and the presence of concurrent driver mutations at baseline could predict clinical benefit of AZD9291 treatment.

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    P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.01-16 - Dynamic ctDNA Monitoring Revealed Novel Resistance Mechanisms and Response Predictors of Osimertinib Treatment in East Asian NSCLC Patients (Now Available) (ID 13861)

      16:45 - 18:00  |  Author(s): Zhihuang Hu

      • Abstract
      • Slides

      Background

      Advanced NSCLC patients, harboring EGFR T790M, exhibit marked diversity in tumor behavior and response to AZD9291, yet a discriminable molecular profile remains elusive. In addition, although EGFRC797S was involved in 30% of AZD9291 resistance cases in Western patients, mechanisms for the rest patients remain unclear, especially for the East Asian population. We utilized circulating tumor DNA (ctDNA) profiling to conduct dynamic monitoring in patients undergoing AZD9291, thus characterizing mutational heterogeneity and genomic evolution.

      Method

      Longitudinal plasma samples were collected before, during and post of the AZD9291 treatment in Chinese NSCLC patients with acquired T790M mutation. A ctDNA panel, spanning 160KB of human genome, was used to perform capture-based targeted sequencing that comprises critical exons and introns of 168 genes. The EGFR mutation abundance and dynamic changes of allele fraction (AF) were analyzed with progression-free survival (PFS) after AZD9291 treatment.

      Result

      A total of 61 samples were collected longitudinally from 14 patients, of which 9 have experienced progressive disease (PD). Six patients exhibited a rebound of ctDNA prior to radiographic PD, suggesting the potential of ctDNA in early detection of PD. Several acquired mutations were detected with the AZD9291 resistance, including newly identified EGFR G796S, L792H/F/R/V, V802F, V843I mutations, expect for the previously reported RB1 and EGFR C797S, L718Q mutations. Patients with a higher ratio of T790M and EGFRactivating mutation at baseline had a significantly longer PFS (9.6m vs 4.5m, p=0.008). A lower ratio of EGFRactivating mutation AF compared to baseline at first follow-up was significantly correlated with a longer PFS (8.5m vs 5.0m, p=0.027). Furthermore, patients harboring other known driver mutations in addition to T790M at baseline had an inferior PFS (4.9m vs 7.8m, P=0.039).

      Conclusion

      Several novel resistance mechanisms were identified by ctDNA monitoring in the East Asian patients treated with AZD9291. Relative AF of T790M, changes of AF after treatment and the presence of concurrent driver mutations at baseline could predict clinical benefit of AZD9291 treatment.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.