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Angela Chan



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    MA07 - Clinical Questions and Potential Blood Markers for Immunotherapy (ID 125)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Immuno-oncology
    • Presentations: 1
    • Now Available
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      MA07.11 - Survival Outcomes Based on Gender of Advanced Nonsmall Cell Lung Cancer Patients Treated with Pembrolizumab or Nivolumab in Everyday Clinical Practice (Now Available) (ID 841)

      13:30 - 15:00  |  Author(s): Angela Chan

      • Abstract
      • Presentation
      • Slides

      Background

      Women are underrepresented in clinical trials of PD1 Ab. We investigated the relationship between gender and overall survival (OS) in aNSCLC patients (pts) treated with PD1 Ab in a large Canadian provincial cohort.

      Method

      All aNSCLC pts treated with nivolumab (NIV) or pembrolizumab (PEM) between 06/2015 and 11/2018 at BC Cancer were identified. Demographic, tumor, treatment details, and survival status were collected from chart review. Kaplan-Meier (KM) curves of OS from initiation of PD1 Ab were generated and compared by the log-rank test.

      Result

      Of 527 pts analyzed (58.9% NIV, 36.1% PEM), 50.5% were female. Women were more likely to have Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0/1 at PD1 Ab initiation (72.9% vs. 64.8%, p=0.05), lower median Charlson Comorbidity Index score (CCI, 2.0 vs. 3.0, p=0.006), and tumors with non-squamous histology (83.5% vs. 69.7%, p<0.001) or Epidermal Growth Factor Receptor (EGFR) mutation (9.8% vs. 3.4%, p=0.006). No significant gender variation in age at diagnosis, smoking status, and programmed death ligand 1 tumor proportion score (PD-L1 TPS) was observed. In addition, there were no differences in type of PD1 Ab, line of treatment, duration of treatment, or treatment discontinuation due to immune related adverse events. With a median follow-up of 16.3 months by reverse KM method, 65% of pts had died. In the entire cohort, women had a longer median OS than men (10.2 vs. 8.1 months, p=0.029). In the subgroup of ECOG PS 2/3 pts, men had worse OS (3.9 vs. 6.5 months, p=0.034). Women ≥60 years of age at initiation of PD1 Ab demonstrated superior median OS to men (12.2 vs. 6.1 months, p=0.006). On multivariable analysis of NIV pts, male gender (HR=1.3, 95% CI 1.0-1.7, p=0.02), baseline ECOG PS 2/3 (HR=2.5, 95% CI=1.9-3.2 p<0.001), CCI score≥3 (HR=1.6, 95% CI=1.3-2.1, p<0.001), and EGFR/ALK aberration (HR=2.3, 95% CI 1.4-3.9, p<0.001) predicted for worse survival; for PEM pts, only ECOG PS 2/3 (HR=2.5, 95% CI 1.6-3.9, p<0.001) was associated with OS.

      Conclusion

      In this large series with a significant proportion of women, females treated with PD1 Ab for aNSCLC lived longer than men (especially if ECOG PS 2/3 or age≥ 60 years.) Despite similarities in smoking status and PD-L1 TPS, gender divergence in outcome could be attributed to more favorable histology and baseline ECOG PS in females. Increased enrollment of women in PD1 Ab trials would facilitate evaluation of gender as a predictive variable.

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    P2.04 - Immuno-oncology (ID 167)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.04-30 - Seq-ing a Better Way to Detect PD-L1 in NSCLC (ID 2534)

      10:15 - 18:15  |  Author(s): Angela Chan

      • Abstract

      Background

      Immunotherapies targeted against PD-L1 and PD-1 have caused a paradigm shift in the treatment of NSCLC, and PD-L1 protein expression has emerged as a standard diagnostic biomarker that predicts which patients are more likely to respond to immunotherapy. However, the use of PD-L1 protein expression as a biomarker is complicated by differences in PD-L1 antibodies, immunohistochemistry methods and platforms, pathologist scoring, and positivity cut-points. We propose that using RNA-sequencing (RNA-seq) methodologies will be an equally reliable approach to determine PD-L1 expression within a tumour and will yield a greater depth of biomarker information than PD-L1 IHC alone.

      Method

      We performed quantitative immunohistochemistry (qIHC) on 262 resected stage I-III formalin-fixed paraffin-embedded (FFPE) NSCLC patient samples registered in the Glans-Look Lung Cancer Research (GLR) database using the commercially available E1L3N PD-L1 antibody (Cell Signalling Technologies). Staining intensity was quantified and used to establish a positivity threshold that was subsequently used to define positivity cut-points of <1%, 1%-49%, and >50% (as used for determining treatment eligibility for Pembrolizumab). We performed single-end RNA-sequencing on FFPE samples from the same GLR patient cohort. Raw counts were normalized to counts-per-million for use in our analyses.

      Result

      We compared the PD-L1 mRNA expression to the PD-L1 protein staining intensity across the tissue core and found a significant correlation (p<0.001, Spearman’s rho=0.538). We also found significant correlation between PD-L1 mRNA expression and the percent-positivity score determined by qIHC (p<0.001, Spearman’s rho=0.605), which was particularly apparent when comparing PD-L1 mRNA expression between cut-point groups where expression was significantly higher in the 1%-49% and >50% groups. Interestingly, we also found moderate, yet significant correlation between PD-1 mRNA expression and both PD-L1 protein staining intensity and percent positivity (p<0.001, Spearman’s rho=0.437 and 0.415 respectively), and we were able to identify several differentially expressed genes between the PD-L1 positive and negative groups.

      Conclusion

      Given the high degree of correlation between PD-L1 mRNA expression and PD-L1 protein staining and positivity, RNA-seq can be a viable option for assessing candidacy for immunotherapy. In addition to the wealth of supplementary data on important biomarkers, RNA-seq offers the possibility for using non-invasive procedures such as liquid biopsy to measure PD-L1 levels in a sequential, objective fashion.