Skip to main content
SpringerLink
Log in

EGFR and PDL1: A Match (Not) Made in Heaven—A Real-World Retrospective Analysis of PDL1 Expression in EGFR-Mutated NSCLC

  • Original Research
  • Published:
Advances in Therapy Aims and scope Submit manuscript

Abstract

Introduction

EGFR (epidermal growth factor receptor) mutant NSCLC (non-small cell lung carcinoma) comprises 35–40% of cases in the Asian NSCLC cohort, compared to 15–20% in the rest of the world. Improved response rates have been observed in terms of PFS (progression-free survival) and ORR (overall response rate) when treated with EGFR TKIs (tyrosine kinase inhibitors). However, resistance eventually ensues regardless of the generation of TKI used. Preclinical studies have reported that PDL1 (programmed death ligand 1) is a downstream target of EGFR and is interposed by IL-6/JAK/STAT3 (interleukin-6/Janus kinase/signal transducer and activator of transcription 3), NF-κB (nuclear factor kappa beta), and p-ERK1/2/p-c-Jun pathways. Hence, it may potentially be repressed by EGFR TKIs. In this retrospective exploratory analysis, we studied whether PDL1 expression affects efficacy of EGFR TKIs and clinical outcome in patients with untreated metastatic EGFR-mutated lung adenocarcinoma.

Methods

This single-center retrospective, exploratory analysis was performed between January 2015 and December 2019. Among 1350 cases of NSCLC, 470 were EGFR mutant, of which PDL1 expression testing was done in 193 patients who were included in this study.

Results

Median age was 60 years (range 24–87 years). A total of 116 patients (60.1%) had inframe deletion in exon 19, 52 (26.9%) had L858R, and 25 (13%) had uncommon mutations. The number of patients with PDL1 tumour proportion score (TPS) < 1% was 109 (56.5%); 1–49%, 57 (29.5%); and ≥ 50%, 27 (14%). Comparing clinical characteristics among various PDL1 groups, there were no statistically significant correlations obtained. However, patients with PDL1 > 50% were smokers, and showed a trend for higher disease burden at diagnosis. Median PFS of PDL1 < 1% was 10.14 months, compared to 9.4 months in the PDL1 > 1% group; however, the values did not reach statistical significance.

Conclusion

The current study was an exploratory retrospective study; however, the results add to the growing body of evidence that PDL1 expression in EGFR-mutated NSCLC does not have any prognostic significance. Also the efficacy of EGFR TKIs is not influenced by variations in PDL1 TPS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Yang JCH, Sequist LV, Mok TS, Schuler M. Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. Lancet Oncol. 2015;16(7):830–8.

    Article  CAS  Google Scholar 

  2. Prabhash K, Advani SH, Batra U, et al. Biomarkers in non-small cell lung cancers: indian consensus guidelines for molecular testing. Adv Ther. 2019;36(4):766–85. https://doi.org/10.1007/s12325-019-00903-y.

    Article  CAS  PubMed  Google Scholar 

  3. National Comprehensive Cancer Network. Non-small cell lung cancer (Version3.2020). https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Published 2020. Accessed 10 Apr 2020.

  4. Chen N, Fang W, Zhan J, et al. Upregulation of PD-L1 by EGFR activation mediates the immune escape in EGFR-driven NSCLC implication for optional immune targeted therapy for NSCLC. JTO Acquis. 2015;10(6):910–23. https://doi.org/10.1097/JTO.0000000000000500.

    Article  CAS  Google Scholar 

  5. Bassanelli M, Sioletic S, Martini M, Giacinti S, Immunotherapy A. Heterogeneity of PD-L1 expression and relationship with biology of NSCLC. Anticancer Res. 2018;3796:3789–96. https://doi.org/10.21873/anticanres.12662.

    Article  CAS  Google Scholar 

  6. Schwartz LH, Litière S, De Vries E, et al. RECIST 11—update and clarification: from the RECIST Committee. Eur J Cancer. 2017. https://doi.org/10.1016/j.ejca.2016.03.081.RECIST.

    Article  Google Scholar 

  7. Brown H, Vansteenkiste J, Nakagawa K, et al. Programmed cell death ligand 1 expression in untreated EGFR mutated advanced NSCLC and response to osimertinib versus comparator in FLAURA. J Thorac Oncol. 2019;15(1):138–43. https://doi.org/10.1016/j.jtho.2019.09.009.

    Article  CAS  PubMed  Google Scholar 

  8. Azuma K, Ota K, Kawahara A, et al. Association of PD-L1 overexpression with activating EGFR mutations in surgically resected nonsmall-cell lung cancer. Ann Oncol. 2014;25(10):1935–40. https://doi.org/10.1093/annonc/mdu242.

    Article  CAS  PubMed  Google Scholar 

  9. Zhang N, Zeng Y, Du W. The EGFR pathway is involved in the regulation of PD-L1 expression via the IL-6/JAK/STAT3 signaling pathway in EGFR-mutated non-small cell lung cancer. Int J Oncol. 2016;3(15):1360–8. https://doi.org/10.3892/ijo.2016.3632.

    Article  CAS  Google Scholar 

  10. Lee JM, Lee SH, Chang, et al. Positive PD-L1 expression is associated with unfavorable clinical outcome in EGFR-mutated lung adenocarcinomas treated with EGFR-TKIs. Eur Respir J. 2019;54:PA367.

  11. Garon EB, Hellmann MD, Rizvi NA, Carcereny E, Leighl NB. Five-year overall survival for patients with advanced non-small-cell lung cancer treated with pembrolizumab: results from the phase I KEYNOTE-001 study abstract. J Clin Med. 2019;37(28):2518–28.

    CAS  Google Scholar 

  12. Jin Y, Shen X, Pan Y, et al. Correlation between PD-L1 expression and clinicopathological characteristics of non-small cell lung cancer: a real-world study of a large Chinese cohort. J Thorac Dis. 2019;1(11):4591–601. https://doi.org/10.21037/jtd.2019.10.80.

    Article  Google Scholar 

  13. Su S, Dong Z, Xie Z, Yan L. Strong programmed death ligand 1 expression predicts poor response and de novo resistance to EGFR tyrosine kinase inhibitors among NSCLC patients with EGFR mutation. J Thorac Oncol. 2018;13(11):1668–75. https://doi.org/10.1016/j.jtho.2018.07.016.

    Article  PubMed  Google Scholar 

  14. Zhang M, Li G, Wang Y, Wang Y, Zhao S, Haihong P. PD-L1 expression in lung cancer and its correlation with driver mutations: a meta-analysis. Sci Rep. 2016;2017:1–10. https://doi.org/10.1038/s41598-017-10925-7.

    Article  CAS  Google Scholar 

  15. Yoon BW, Chang B, Lee SH. High PD-L1 expression is associated with unfavorable clinical outcome in EGFR-mutated lung adenocarcinomas treated with targeted therapy. Onco Targets Ther. 2020;13:8273–85. https://doi.org/10.2147/OTT.S271011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Funding

No funding or sponsorship was received for this study or publication of this article.

Authorship

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Disclosures

All authors (Ullas Batra, Mansi Sharma, Shrinidhi Nathany, Abhishek Bansal, Sunil Pasricha, Parveen Jain, Anurag Mehta, Harkirat Singh) have nothing to disclose.

Compliance with Ethics Guidelines

This study has been approved by the Rajiv Gandhi Cancer Institute and Research Centre Institutional Review Board (Res/SCM/26/2018/21) and has been carried out in compliance with the declaration of Helsinki.

Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Author information

Authors and Affiliations

  1. Department of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, 110085, India

    Ullas Batra, Mansi Sharma, Parveen Jain & Harkirat Singh

  2. Molecular Diagnostics, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, 110085, India

    Shrinidhi Nathany

  3. Radiology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, 110085, India

    Abhishek Bansal

  4. Pathology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, 110085, India

    Sunil Pasricha

  5. Laboratory Services, Molecular Diagnostics and Transfusion Medicine, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, 110085, India

    Anurag Mehta

Authors
  1. Ullas Batra
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mansi Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shrinidhi Nathany
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Abhishek Bansal
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sunil Pasricha
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Parveen Jain
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Anurag Mehta
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Harkirat Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ullas Batra.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Batra, U., Sharma, M., Nathany, S. et al. EGFR and PDL1: A Match (Not) Made in Heaven—A Real-World Retrospective Analysis of PDL1 Expression in EGFR-Mutated NSCLC. Adv Ther 38, 1791–1800 (2021). https://doi.org/10.1007/s12325-021-01655-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12325-021-01655-4

Keywords

Search

Navigation