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Cited by 960Cancer Immunotherapy and BiomarkersImmunotherapy and Immune ResponsesT-cell and B-cell Immunology

The role of PD-L1 expression as a predictive biomarker: an analysis of all US Food and Drug Administration (FDA) approvals of immune checkpoint inhibitors

Open access
Davis, Andrew A., Patel, Vaibhav G.·2019·Journal for ImmunoTherapy of Cancer
DOI 10.1186/s40425-019-0768-9PMC PMC6815032
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Abstract

The development of immune checkpoint inhibitors has changed the treatment paradigm for advanced cancers across many tumor types. Despite encouraging and sometimes durable responses in a subset of patients, most patients do not respond. Tumors have adopted the PD-1/PD-L1 axis for immune escape to facilitate tumor growth, which can be leveraged as a potential target for immune checkpoint inhibitors. On this basis, PD-L1 protein expression on tumor or immune cells emerged as the first potential predictive biomarker for sensitivity to immune checkpoint blockade. The goal of our study was to evaluate PD-L1 as a predictive biomarker based on all US Food and Drug Administration (FDA) drug approvals of immune checkpoint inhibitors. We evaluated the primary studies associated with 45 FDA drug approvals from 2011 until April 2019. In total, there were approvals across 15 tumor types. Across all approvals, PD-L1 was predictive in only 28.9% of cases, and was either not predictive (53.3%) or not tested (17.8%) in the remaining cases. There were 9 FDA approvals linked to a specific PD-L1 threshold and companion diagnostic: bladder cancer (N = 3), non-small cell lung cancer (N = 3), triple-negative breast cancer (N = 1), cervical cancer (N = 1), and gastric/gastroesophageal junction cancer (N = 1) with 8 of 9 (88.9%) with immune checkpoint inhibitor monotherapy. The PD-L1 thresholds were variable both within and across tumor types using several different assays, including approvals at the following PD-L1 thresholds: 1, 5, and 50%. PD-L1 expression was also measured in a variable fashion either on tumor cells, tumor-infiltrating immune cells, or both. In conclusion, our findings indicate that PD-L1 expression as a predictive biomarker has limitations and that the decision to pursue testing must be carefully implemented for clinical decision-making.

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  • High TMB and immune checkpoint molecule expression, including PD-L1, have limited clinical utility as predictive biomarkers when considered in isolation.

    “While high TMB and immune checkpoint molecule expression, including PD-L1, have been used as predictive biomarkers across different cancer types, they have limited clinical utility when considered in isolation88,101.”

    From Multi-omic analysis of hepatocellular carcinoma reveals aberrant cis-regulatory changes and dysregulated retrotransposons with prognostic potential (2025) · cites this paper as [101]

    The Discussion describes PD-L1 as an imprecise predictive biomarker and says its clinical use depends on the FDA-approved setting. It also identifies implementation challenges for TMB, but does not establish that high TMB has limited clinical utility when considered in isolation. The paper does not evaluate other immune checkpoint molecules as predictive biomarkers. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Studies reveal a lack of correlation between the level of PD-L1 expression and the response to ICI treatment in certain cancers.

    “Studies reveal a lack of correlation between the level of PD-L1 expression and the response to ICI treatment in certain cancers (Davis and Patel, 2019; Li et al., 2022).”

    From Microphysiological systems as models for immunologically ‘cold’ tumors (2024) · cites this paper as Davis and Patel, 2019

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Cited by

Sorted by citations

Authors
Davis, A. A., & Patel, V. G.
Affiliations
  • Northwestern University (US)
  • Tisch Cancer Institute (US)
Corresponding author
Patel, Vaibhav G.
ORCID
Venue
Journal for ImmunoTherapy of Cancer
Publisher
BMJ
Published
2019-10-26
Volume
7
Issue
1
Pages
278-278
ISSN
2051-1426 (ISSN-L)
DOI
10.1186/s40425-019-0768-9
PMC
PMC6815032
OpenAlex
W2981790403
Cited by
960
References
8
Citations by year
2026: 76 · 2025: 116 · 2024: 145 · 2023: 153 · 2022: 204 · 2021: 161 · 2020: 105
FWCI
49.95
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal for ImmunoTherapy of Cancer (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords
PD-L1 expression, predictive biomarkers, immune checkpoint inhibitors, FDA drug approval, companion diagnostics, tumor-infiltrating immune cells, immune evasion, PD-1/PD-L1 axis, cancer immunotherapy, non-small cell lung cancer, bladder cancer, triple-negative breast cancer, cervical cancer, gastric cancer
MeSH terms
Antineoplastic Agents, Immunological, Humans, Neoplasms, Prognosis, Biomarkers, Tumor, United States, United States Food and Drug Administration, Gene Expression, Drug Approval, Molecular Targeted Therapy, B7-H1 Antigen

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