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FeedbackProgrammed death-ligand 1 (PD-L1) is an immune-related biomarker that can be expressed on the surface of many tissue types, including tumor cells. For certain types and stages of cancer, testing for PD-L1 expression may help to identify patients most likely to benefit from treatment with PD-L1 inhibitors. Novel immunotherapies, known as immune checkpoint inhibitors, can interrupt signals generated by immune checkpoint proteins, such as PD-L1, and enhance antitumor T-cell immunity. Several PD-L1 inhibitors, including atezolizumab, durvalumab, nivolumab, and pembrolizumab, have been approved for a number of clinical indications and are being evaluated in multiple malignancies. The U.S. Food and Drug Administration (FDA) divides PD-L1 immunohistochemistry (IHC) tests into two groups: companion diagnostics, which provide information that is essential for the safe and effective use of a drug (test results are required for drug use), and complementary or codiagnostic tests, which may be used in treatment selection but are not considered essential for use of the corresponding therapy (test results are NOT required for drug use).
Quick Answers for Clinicians
COMPANION programmed death-ligand 1 (PD-L1) testing is shown to be predictive of patient response to a specific immunotherapy for a type of tumor, on a specific platform. Testing is required for the specific immunotherapy to be used. COMPLEMENTARY PD-L1 testing may be predictive of patient response to a specific immunotherapy for a type of tumor, but this testing is not required to use immunotherapy.
Selection of the appropriate test depends on the patient’s malignancy and the intended use of the programmed death-ligand 1 (PD-L1) inhibitor. Refer to the PD-L1 Testing by Sample Type and Drug table for tests that are available for specific cancer types.
Indications for Testing
PD-L1 testing may be considered for patients with specific types of malignancies to predict response to specific immune checkpoint inhibitors.
PD-L1 Laboratory Testing
PD-L1 testing recommendations depend on the agent being considered for use, the malignancy, and the stage of cancer in question. Please refer to the specific drug package inserts in the table below for complete clinical indications.
There are also several interpretive scoring systems available, including the tumor proportion score (TPS), the combined positive score (CPS), and tumor-infiltrating immune cell (IC) staining assessments. The selection of which scoring system to use, as well as the interpretive cutoffs, depends on the test, tumor, and indications. In brief, the TPS is based on the proportion of tumor cells that express PD-L1. The CPS is calculated in a manner similar to that used for the TPS, but includes PD-L1 expression in tumor-associated lymphocytes and macrophages, as well as tumor cells, over the total number of tumor cells (staining and nonstaining). The SP142 assay has two different scoring systems; one uses a stepwise approach based on tumor cell and tumor-infiltrating IC staining assessments, and the second uses a tumor-infiltrating IC staining algorithm that calculates the proportion of the tumor area represented by PD-L1-expressing ICs. Refer to the interpretation manuals provided by the manufacturer because updates are frequently released.
| Sample Type | Drug Under Consideration | PD-L1 Test | Additional Resources |
|---|---|---|---|
| Breast carcinoma (triple negative) | Pembrolizumab (KEYTRUDA) and chemotherapy | PD-L1 22C3 IHC with Combined Positive Score (CPS) Interpretation, pembrolizumab (KEYTRUDA) 3000197 (COMPANION testing) | |
| Cervical carcinoma (including cervical squamous cell carcinoma and endocervical adenocarcinoma) | Pembrolizumab (KEYTRUDA) | PD-L1 22C3 IHC with Combined Positive Score (CPS) Interpretation, pembrolizumab (KEYTRUDA) 3000197 (COMPANION testing) | Assay approval informationb |
| Esophageal squamous cell carcinoma | Pembrolizumab (KEYTRUDA) | PD-L1 22C3 IHC with Combined Positive Score (CPS) Interpretation, pembrolizumab (KEYTRUDA) 3000197 (COMPANION testing) | |
| Head and neck squamous cell carcinoma |
PD-L1 22C3 IHC with Combined Positive Score (CPS) Interpretation, pembrolizumab (KEYTRUDA) 3000197 (COMPANION testing) |
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| Nivolumab (OPDIVO) | PD-L1 28-8 pharmDx by Immunohistochemistry with Interpretation, nivolumab (OPDIVO) 2013684 (COMPLEMENTARY testing) | ||
| NSCLC | Pembrolizumab (KEYTRUDA) | PD-L1 22C3 IHC with Tumor Proportion Score (TPS) Interpretation, pembrolizumab (KEYTRUDA) and cemiplimab-rwlc (LIBTAYO) 2013284 (COMPANION testing) | Treatment indications |
| Cemiplimab-rwlc (LIBTAYO) | PD-L1 22C3 IHC with Tumor Proportion Score (TPS) Interpretation, pembrolizumab (KEYTRUDA) and cemiplimab-rwlc (LIBTAYO) 2013284 (COMPANION testing) | ||
| Nivolumab (OPDIVO) plus ipilimumab (YERVOY) | PD-L1 28-8 pharmDx by Immunohistochemistry with Interpretation, nivolumab (OPDIVO) 2013684 (COMPANION testing) |
Treatment indications (OPDIVO) Treatment indications (YERVOY) Assay approval informationb |
|
| Nivolumab (OPDIVO) | PD-L1 28-8 pharmDx by Immunohistochemistry with Interpretation, nivolumab (OPDIVO) 2013684 (nonsquamous NSCLC only) (COMPLEMENTARY testing) | ||
| Atezolizumab (TECENTRIQ) |
PD-L1 SP142 for treatment with atezolizumab (TECENTRIQ) (COMPLEMENTARY testing; not currently performed at ARUP Laboratories) OR PD-L1 SP263 for treatment with atezolizumab (TECENTRIQ) (COMPANION testing; not currently performed at ARUP Laboratories) |
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| Atezolizumab (TECENTRIQ) and chemotherapy |
PD-L1 SP142 for treatment with atezolizumab (TECENTRIQ) (COMPLEMENTARY testing; not currently performed at ARUP Laboratories) |
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| Urothelial carcinoma | Atezolizumab (TECENTRIQ) | PD-L1 SP142 for treatment with atezolizumab (TECENTRIQ) (COMPANION testing; not currently performed at ARUP Laboratories) | |
| Nivolumab (OPDIVO) | PD-L1 28-8 pharmDx by Immunohistochemistry with Interpretation, nivolumab (OPDIVO) 2013684 (COMPLEMENTARY testing) | Assay approval informationb | |
|
aAtezolizumab (TECENTRIQ), cemiplimab-rwlc (LIBTAYO), ipilimumab (YERVOY), nivolumab (OPDIVO), and pembrolizumab (KEYTRUDA) may be used to treat other types of cancer, but PD-L1 testing is only indicated for the sample types listed above. For more information, see the treatment indications for each drug. bFDA approval information can be found by searching for the specific assay in this database. NSCLC, non-small cell lung cancer |
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ARUP Laboratory Tests
Use for NSCLC specimens only
Companion diagnostic testing to aid in the prediction of response to pembrolizumab (KEYTRUDA) as first- or second-line monotherapy in patients with NSCLC (for patients with advanced NSCLC whose tumors have a TPS of ≥1%) or to cemiplimab-rwlc (LIBTAYO) as first-line treatment (for patients with advanced NSCLC whose tumors have a TPS of ≥50%)
Use for cervical, esophageal squamous cell carcinoma (ESCC), head and neck squamous cell carcinoma (HNSCC), or triple-negative breast cancer specimens only to aid in prediction of response to pembrolizumab (KEYTRUDA)
Immunohistochemistry
FDA-approved companion diagnostic testing to aid in predicting the overall survival benefit from nivolumab (OPDIVO) in combination with ipilimumab (YERVOY) as first-line therapy for patients with NSCLC
FDA-approved complementary codiagnostic test that may aid in predicting response to nivolumab (OPDIVO) treatment for patients with nonsquamous NSCLC, urothelial carcinoma, or HNSCC
Immunohistochemistry
References
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Massard C, Gordon MS, Sharma S, et al. Safety and efficacy of durvalumab (MEDI4736), an anti-programmed cell death ligand-1 immune checkpoint inhibitor, in patients with advanced urothelial bladder cancer. J Clin Oncol. 2016;34(26):3119-3125.
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Udall M, Rizzo M, Kenny J, et al. PD-L1 diagnostic tests: a systematic literature review of scoring algorithms and test-validation metrics. Diagn Pathol. 2018;13(1):12.
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USFDA - Medical Devices: In Vitro Diagnostics
U.S. Food and Drug Administration. Medical devices: in vitro diagnostics. [Last updated: Dec 2018; Accessed: Apr 2022]
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USFDA - KEYTRUDA package insert
U.S. Food and Drug Administration. KEYTRUDA package insert. [Revised: Mar 2022; Accessed: Mar 2022]
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USFDA - Premarket approval database
U.S. Food and Drug Administration. Premarket approval (PMA) database. [Revised: Jun 2022; Accessed: Jun 2022]
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USFDA - OPDIVO package insert
U.S. Food and Drug Administration. OPDIVO package insert. [Revised: Mar 2022; Accessed: Mar 2022]
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USFDA - LIBTAYO package insert
U.S. Food and Drug Administration. LIBTAYO package insert. [Revised: Feb 2021; Accessed: Mar 2022]
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USFDA - YERVOY package insert
U.S. Food and Drug Administration. YERVOY package insert. [Revised: Feb 2022; Accessed: Mar 2022]
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USFDA - TECENTRIQ package insert
U.S. Food and Drug Administration. TECENTRIQ package insert. [Updated Oct 2021; Accessed: Mar 2022]
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