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Haocheng Li



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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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      P3.13-28 - Heterogeneity, Prevalence and Prognostic Significance of PDL1 Expression in Early Resected NSCLC (ID 14335)

      12:00 - 13:30  |  Author(s): Haocheng Li

      • Abstract
      • Slides

      Background

      The interaction between the programmed death protein-1 receptor (PD1) and its membrane-bound ligand (PDL1) is one mechanism by which tumor cells evade the immune system. Cancer immunotherapies target this interaction by blocking the function of either protein, allowing for T-cell activation and destruction of the tumor. Because PDL1 expression in tumor is used to identify patients who might benefit from immune-modulating treatment, its detection plays a key role in clinical recommendations. Our objectives are to assess the prevalence of PDL1 expression in early stage non-small cell lung cancer (NSCLC) patients, determine its association with clinical outcomes using the Glans-Look Research (GLR) database (Calgary, AB), and validate these findings using a cohort from the Manitoba Tumor Bank (MBTB).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A tissue microarray (TMA) was built using pre-treatment resected and biopsy tissue samples from 459 GLR database patients with early stage NSCLC, diagnosed between 2003 and 2010. Cell lines expressing varying levels of PDL1 were generated, embedded into HistoGel™ and co-mounted onto the GLR and MBTB arrays. Fluorescence immunohistochemistry was performed using anti-PDL1 E1L3N (Cell Signaling Technology), and PDL1 expression was evaluated as percent-positive and intensity scores in the cytoplasmic compartment of tumor and stromal cells using HALO™ automated image analysis software. Cell line PDL1 intensity scores served as on-slide reference standards to normalize PDL1 expression in patient specimens using R Programming software. PDL1-percent-positive tumor scores were generated to assess the cut-points of ≥50%(“PDL1-strong”), ≥1%-to-49%(“PDL1-weak”), and <1%(“PDL1-negative”), indicated by the FDA-approved companion diagnostic anti-PDL1 22C3 (Dako) for pembrolizumab. Clinicopathological outcomes were analyzed, and overall survival was assessed using the Kaplan-Meier method and compared using the log-rank test.

      4c3880bb027f159e801041b1021e88e8 Result

      Preliminary analyses indicate PDL1-weak/negative GLR patients with adenocarcinoma experienced higher median OS (3.50yrs) compared to PDL1-strong patients (1.91yrs) (p=0.0043). This trend was not significant over all histologies, or when using mean scores. The opposite trend was found with the MBTB cohort (2.52yrs vs. 1.76yrs OS, PDL1-strong vs. PDL1-weak/negative maximum scores, p=0.0410).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Variations across datasets illustrate the difficulty in harmonizing PDL1 testing. Heterogeneity of protein expression, TMA sampling error, and differences between study cohorts can translate into variable correlations between PDL1-positivity and survival estimates. Increased survivorship in GLR adenocarcinoma patients with PDL1-weak/negative staining could challenge the notion of using PDL1 as a prognostic biomarker. Comparisons between the E1L3N and 22C3 anti-PDL1 assays will be performed, E1L3N percent-positive cut-points will be refined according to the lowest intensity-based statistical p-value, and further outcome findings will be presented and discussed.

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