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Nick Pavlakis



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    ES29 - Advances in Omics - Next Generation (ID 242)

    • Event: WCLC 2020
    • Type: Educational Session
    • Track: Tumor Biology and Systems Biology - Basic and Translational Science
    • Presentations: 1
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      ES29.02 - Chair (ID 4099)

      15:30 - 16:30  |  Presenting Author(s): Nick Pavlakis

      • Abstract

      Abstract not provided

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    IS09 - Industry Symposium Sponsored by Pfizer Oncology: Expert Question Time: ALK+ NSCLC (ID 286)

    • Event: WCLC 2020
    • Type: Industry Symposium
    • Track:
    • Presentations: 1
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      IS09.02 - Selecting Treatment and Management of ALK+ NSCLC (ID 4375)

      13:00 - 14:00  |  Presenting Author(s): Nick Pavlakis

      • Abstract

      Abstract not provided

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    P76 - Targeted Therapy - Clinically Focused - EGFR (ID 253)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Targeted Therapy - Clinically Focused
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P76.08 - High Tumour PD-L1 Is Associated With Poor Outcomes in EGFR-Mutant Lung Cancer Treated With First Generation EGFR TKIs (ID 951)

      00:00 - 00:00  |  Author(s): Nick Pavlakis

      • Abstract
      • Slides

      Introduction

      Approximately 10% of patients with metastatic EGFR-mutant NSCLC exhibit de novo resistance to 1st generation tyrosine kinase inhibitors (TKIs). Apart from the upfront presence of resistance mutations such as T790M, there are no established predictive biomarkers for poor response to TKIs. It has been observed that high tumour PD-L1 expression is associated with poor response to EGFR TKIs in some but not all retrospective series. This study sought to determine the relationship between patients’ outcome treated with 1st line EGFR TKI, and baseline PD-L1 tumour proportional score (TPS) in a large multicentre retrospective series of patients with EGFR-mutant lung cancer.

      Methods

      Patients with Stage IIIB/IV lung adenocarcinoma harbouring a sensitising mutation in EGFR and treated with first-line, first or second generation TKI at five large metropolitan hospitals in Sydney between 2013-2019 were included. PD-L1 TPS was determined using the Ventana anti-PD-L1 (SP263) assay in a NATA-accredited laboratory on a pre-treatment biopsy. High PD-L1 expression is defined as TPS ≥50%; low expression TPS 1 – 49%; and negative PD-L1 TPS <1%. Clinico-pathological information was collected from institutional medical records, and treatment response, progression and survival were investigator-assessed. Determinants of progression and survival hazards were modelled using Cox regression with censoring at dates of last follow-up.

      Results

      Of the 168 included patients, mean age was 67 years, 66% female, and 46% of Caucasian ethnicity. Twenty-eight percent received 1st line gefitinib, 70% received erlotinib and 2% received afatanib. Compared to patients with PD-L1 low/negative tumours (n=145, 86%, those with high PD-L1 (n=23; 14%) had significantly shorter PFS (6.6 vs 13.0 months, HR 2.6 95% CI 1.6-4.2, p<0.0001) and OS (11.5 vs 32.9 months, HR 3.3, 95% CI 1.9-5.7, p<0.0001) and also on multivariate analyses after adjusting for age, ECOG, ethnicity, type of TKI, EGFR mutation type and metastatic sites (p<0.0001). PFS and OS were not significantly different in patients with PD-L1 positive tumours (≥1%) versus PD-L1 negative tumours. High PD-L1 in post-TKI progression biopsies was not associated with poorer outcome compared to low PD-L1 in post-progression biopsies. screen shot 2020-08-27 at 11.34.20 pm.png

      Conclusion

      In this large real-world cohort of patients with EGFR mutant NSCLC, high PD-L1 expression was associated with early resistance to 1st generation EGFR TKIs, and predicts shorter survival. Next generation sequencing of exceptional and poor responders with low vs high PD-L1 is underway to explore molecular mechanisms that may drive PD-L1 expression or non-response to TKIs.

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