PD-L1: Test Selection Guide

This Test Guide provides an overview of the use of tests for PD-L1 and other biomarkers involved in selection of PD-1/PD-L1 inhibitor therapy.

Test Guide

PD-L1

Test Selection Guide

Immune checkpoint inhibitors are a type of cancer immunotherapy, a class of drugs that harnesses the immune system to attack tumor cells. These drugs target immune checkpoint proteins, including programmed death-ligand 1 (PD-L1) and its receptor, programmed cell death protein 1 (PD-1). These proteins normally protect healthy cells from the cytotoxic effects of T cells. However, some tumor cells express PD-L1, which helps them escape the immune response by exhausting responding T cells.1 PD-1/PD-L1 inhibitors “release the brakes” on these responding T cells and have antitumor activity in many types of tumors.1 Assessing predictive biomarkers, primarily PD-L1 expression in the tumor, can help identify patients who are most likely to benefit from PD-1/PD-L1–inhibitor therapy.2 In general, PD-L1 expression in the tumor is associated with better response to PD-1/PD-L–inhibitor therapy.3

Eight PD-1/PD-L1 inhibitors are available, but PD-L1 testing is currently only required for 4: pembrolizumab, nivolumab, atezolizumab, and cemiplimab. Testing requirements vary by the indication for each inhibitor being considered. For some indications, PD-L1 testing is not required to initiate the therapy; for others, a specific PD-L1 immunohistochemical assay is either approved by the US Food and Drug Administration (FDA) as a companion diagnostic or recommended as a complementary diagnostic (Table 1).2,4–16 Each assay uses specific measures and thresholds of PD-L1 expression, which can also vary by indication.2,12–15 The appropriate drug prescribing information and test package insert should be consulted for further information on use and limitations of use.

Microsatellite instability (MSI; test code 14989), mismatch repair deficiency (dMMR; test code 91332), and tumor mutational burden (TMB; test code 12354) are additional biomarkers that can be used to help identify patients who may benefit from PD-1/PD-L1–inhibitor therapy.2 The increased frequency of mutations in MSI-high (MSI-H), dMMR, and TMB-high (TMB-H) tumors can help T cells identify tumor cells as targets and generate a stronger antitumor response.1,2

The tables in this Test Guide provide an overview of the use of tests for PD-L1 and other biomarkers involved in selection of PD-1/PD-L1–inhibitor therapy (Table 2, Table 3). Immune checkpoint inhibition is a rapidly advancing field. Thus, the most recent drug prescribing information, test package insert, and guidelines should be consulted for the most current information. This Test Guide is provided for informational purposes only and is not intended as medical advice. Test selection and interpretation, diagnosis, and patient management decisions should be based on the physician’s education, clinical expertise, and assessment of the patient. If the ordering/treating physician has any questions, please contact our Oncology Client Services at 1.866.894.6920.

Table 1. Summary of Testing Indications and Requirements With FDA-approved PD-L1 Clonesa

Clone
Disease	Therapy	Indications and PD-L1 testing requirements
PD-L1 IHC 22C3 pharmDx12
NSCLC	Keytruda® (pembrolizumab),6 see test code 93279 in Table 2 for test information	PD-L1 testing required (companion diagnostic) 1st-line treatment for PD-L1+ (TPS ≥1%) stage III (not eligible for resection or chemoradiation) or metastatic disease (no EGFR or ALK aberrations) Treatment for PD-L1+ (TPS ≥1%) metastatic disease with progression on or after platinum-based therapy (no EGFR or ALK aberrations, or with progression after treatment for EGFR or ALK aberrant disease) PD-L1 testing indicated but not required 1st-line treatment (combo) for metastatic nonsquamous disease (no EGFR or ALK aberrations) 1st-line treatment (combo) for metastatic squamous disease Treatment (adjuvant) for stage IB (tumor size ≥4 cm), II, or IIIA disease after resection and platinum-based chemotherapy
NSCLC	Libtayo® (cemiplimab),7 see test code 93279 in Table 2 for test information	PD-L1 testing required (companion diagnostic) 1st-line treatment for highly PD-L1+ (TPS ≥50%) advanced (not eligible for resection or chemoradiation) or metastatic disease (no EGFR, ALK, or ROS1 aberrations)
Cervical cancer	Keytruda® (pembrolizumab),6 see test code 36260 in Table 2 for test information	PD-L1 testing required (companion diagnostic) Treatment (combo) for PD-L1+ (CPS ≥1) persistent, recurrent, or metastatic disease Treatment for PD-L1+ (CPS ≥1) recurrent or metastatic disease with progression on or after chemotherapy
ESCC	Keytruda® (pembrolizumab),6 see test code 36260 in Table 2 for test information	PD-L1 testing required (companion diagnostic) Treatment for PD-L1+ (CPS ≥10) advanced or metastatic disease after ≥1 lines of therapy (not amenable for resection or chemoradiation) PD-L1 testing indicated but not required Treatment (combo) for advanced or metastatic disease (not amenable for resection or chemoradiation)
HNSCC	Keytruda® (pembrolizumab),6 see test code 36260 in Table 2 for test information	PD-L1 testing required (companion diagnostic) 1st-line treatment for PD-L1+ (CPS ≥1) metastatic or unresectable recurrent disease PD-L1 testing indicated but not required 1st-line treatment (combo) for metastatic or unresectable recurrent disease Treatment for metastatic or recurrent disease with progression on or after platinum-based therapy
TNBC	Keytruda® (pembrolizumab),6 see test code 36260 in Table 2 for test information	PD-L1 testing required (companion diagnostic) Treatment (combo) for PD-L1+ (CPS ≥10) locally recurrent unresectable or metastatic disease PD-L1 testing indicated but not required Treatment (combo, adjuvant) for high-risk early-stage disease after resection
Gastric/GEJ adenocarcinoma	Keytruda® (pembrolizumab),6 see test code 36260 in Table 2 for test information	PD-L1 testing indicated but not required 1st-line treatment (combo) for advanced unresectable or metastatic HER2+ disease 1st-line treatment (combo) for PD-L1+ (CPS ≥10) HER2-diseaseb
Ventana PD-L1 SP14214
NSCLC	Tecentriq® (atezolizumab),9 see test code 94480 in Table 2 for test information	PD-L1 testing required (companion diagnostic) 1st-line treatment for PD-L1+ (TC ≥50% or IC ≥10%) metastatic disease (no EGFR or ALK aberrations) PD-L1 testing indicated but not required 1st-line treatment (combo) for metastatic non-squamous disease (no EGFR or ALK aberrations) Treatment for metastatic disease with progression on or after platinum-based therapy (no EGFR or ALK aberrations, or with progression after treatment for EGFR- or ALK-aberrant disease)
PD-L1 IHC 28-8 pharmDx13
NSCLC	Opdivo® (nivolumab),8 see test code 93359 in Table 2 for test information	PD-L1 testing required (companion diagnostic) 1st-line treatment (combo) for PD-L1+ (expression ≥1%) metastatic disease (no EGFR or ALK aberrations) PD-L1 testing optional (complementary diagnostic) Treatment for non-squamous NSCLC PD-L1 testing indicated but not required Treatment (neoadjuvant and combo) for resectable (tumors ≥4 cm or node positive) disease 1st-line treatment (combo) for recurrent or metastatic disease (no EGFR or ALK aberrations) Treatment for metastatic disease with progression on or after platinum-based therapy (no EGFR or ALK aberrations, or with progression after treatment for EGFR- or ALK-aberrant disease)
HNSCC	Opdivo® (nivolumab),8 see test code 93793 in Table 2 for test information	PD-L1 testing optional (complementary diagnostic) Treatment for recurrent or metastatic disease with progression on or after platinum-based therapy
Urothelial carcinoma	Opdivo® (nivolumab),8 see test code 93793 in Table 2 for test information	PD-L1 testing optional (complementary diagnostic) Treatment for advanced or metastatic disease with progression on or after platinum-based therapy PD-L1 testing indicated but not required Treatment (adjuvant) after resection if high risk of recurrence
Ventana PD-L1 SP26315,c
NSCLC	Tecentriq® (atezolizumab)9	PD-L1 testing required (companion diagnostic) Treatment (adjuvant) for PD-L1+ (TC ≥1%) stage II to IIIA disease after resection and platinum-based therapy
NSCLC	Libtayo® (cemiplimab)7	PD-L1 testing indicated but not required 1st-line treatment (combo) for advanced (not eligible for resection or chemoradiation) or metastatic disease (no EGFR, ALK, or ROS1 aberrations)

CPS, combined positive score; ESCC, esophageal squamous-cell carcinoma; GEJ, gastroesophageal junction; HNSCC, head and neck squamous-cell carcinoma; IC, immune cells; IHC, immunohistochemistry; NSCLC, non–small-cell lung cancer; PD-L1, programmed death-ligand 1; TC, tumor cells; TNBC, triple-negative breast cancer; TPS, tumor proportion score.
a	This table is only intended as a summary for convenience. The appropriate drug prescribing information and test package insert should be consulted for further information on use and limitations of use.
b	The American Society of Clinical Oncology (ASCO) recommends testing PD-L1 expression for this indication.17
c	FDA-approved PD-L1 testing with clone SP263 for NSCLC is only available through PhenoPath. Contact Oncology Client Services at 1.866.894.6920 or refer to the PhenoPath test menu (http://phenopath.com/test-menu) for test information.

Table 2. Tests Available for Assessing PD-L1 Expression

Test code	Test name	Clinical use	Method and interpretation
PD-L1, clone 22C3 (Keytruda [pembrolizumab] and Libtayo [cemiplimab])
93279	PD-L1 Lung (Pembrolizumab or Cemiplimab), IHC	Identify patients with NSCLC who may be eligible for treatment with pembrolizumab or cemiplimaba	PD-L1 protein expression is determined using an IHC method (22C3). Results are based on TPS, which is the percentage of viable tumor cells showing partial or complete membrane staining. The specimen is considered PD-L1–positive if TPS is ≥1% (for pembrolizumab) or ≥50% (for cemiplimab).12
36260	PD-L1 Non-Lung (Pembrolizumab), IHC	Identify patients with non-NSCLC tumor typesb who may be eligible for treatment with pembrolizumaba	PD-L1 protein expression is determined using an IHC method (22C3). Results are based on CPS, which is the number of PD-L1–staining cells (for tumor cells, partial or complete membrane staining; for lymphocytes and macrophages, membrane and/or cytoplasmic staining) divided by the number of viable tumor cells, multiplied by 100. The specimen is considered PD-L1–positive if CPS is ≥1 (cervical cancer, HNSCC) or ≥10 (ESCC, TNBC).12
PD-L1, clone SP142 (Tecentriq [atezolizumab])
94480	PD-L1 Lung (Atezolizumab), IHC	Identify patients with NSCLC who may be eligible for treatment with atezolizumaba	PD-L1 protein expression is determined using an IHC method (SP142). Results are based on TC, which is the percentage of tumor cells showing partial or complete membrane staining, or IC, which is the percentage of tumor area covered by PD-L1–staining tumor-infiltrating immune cells. The specimen is considered PD-L1–positive if TC ≥50% or IC ≥10%.14
PD-L1, clone 28-8 (Opdivo [nivolumab])
93359	PD-L1 Lung (Nivolumab), IHC	Identify patients with NSCLC who may be eligible for treatment with nivolumab combination therapya Identify patients with non-squamous NSCLC who may have enhanced survival if treated with nivolumab	PD-L1 protein expression is determined using an IHC method (28-8). Results are based on % PD-L1 expression, which is the percentage of viable tumor cells showing partial or complete membrane staining. The specimen is considered PD-L1–positive if PD-L1 expression is ≥1%.13
93793	PD-L1 Non-Lung (Nivolumab), IHC	Identify patients with non-NSCLC tumor typesc who may have enhanced survival or response rate if treated with nivolumab	PD-L1 protein expression is determined using an IHC method (28-8). Results are based on % PD-L1 expression, which is the percentage of viable tumor cells showing partial or complete membrane staining. The specimen is considered PD-L1–positive if PD-L1 expression is ≥1% (HNSCC, urothelial carcinoma).13
PD-L1, generic
94007	PD-L1, IHC With Interpretationc	Detect PD-L1 expression in cancersd	PD-L1 protein expression is determined using an IHC method (SP263). Results are based on % TC, and % IC (when applicable).

CPS, combined positive score; ESCC, esophageal squamous-cell carcinoma; GEJ, gastroesophageal junction; HNSCC, head and neck squamous-cell carcinoma; IC, immune cells; IHC, immunohistochemistry; NSCLC, non–small-cell lung cancer; PD-L1, programmed death-ligand 1; TC, tumor cells; TNBC, triple-negative breast cancer; TPS, tumor proportion score.
a	Documentation of PD-L1 expression on tumor cells and/or tumor-infiltrating immune cells using an FDA-approved test is a prerequisite for treatment with the indicated therapy.
b	This test currently is applicable only to specific tumor types.
c	This test was developed and its analytical performance characteristics have been determined by Quest Diagnostics. It has not been cleared or approved by the US FDA. This assay has been validated pursuant to the CLIA regulations and is used for clinical purposes.
d	FDA-approved PD-L1 testing with clone SP263 for NSCLC is only available through PhenoPath. The specimen is considered PD-L1–positive if TC ≥50% for Libtayo (cemiplimab) or TC ≥1% for Tecentriq (atezolizumab). Contact Oncology Client Services at 1.866.894.6920 or refer to the PhenoPath test menu (http://phenopath.com/test-menu) for test information.

Table 3. Other Tests Available to Guide the Selection of PD-1/PD-L1–Inhibitor Therapy

Test code	Test name	Clinical use
MSI
14989	Microsatellite Instability (MSI)a	Identify patients with unresectable or metastatic solid tumors who may be eligible for treatment with PD-1/PD-L1 targeted therapy
dMMR
91332	Lynch Syndrome Tumor Panel, IHC with Interpretation Includes MLH1 (test code 70196), MSH2 (test code 70197), MSH6 (test code 16938), and PMS2 (test code 16997).	Identify patients with unresectable or metastatic solid tumors who may be eligible for treatment with PD-1/PD-L1 targeted therapy
TMB
12354	Tumor Mutation Burdena	Identify patients with unresectable or metastatic solid tumors who may be eligible for treatment with PD-1/PD-L1 targeted therapy

dMMR, deficient mismatch repair; IHC, immunohistochemistry; MSI, microsatellite instability; TMB, tumor mutational burden.
a	This test was developed and its analytical performance characteristics have been determined by Quest. It has not been cleared or approved by the US FDA. This assay has been validated pursuant to the CLIA regulations and is used for clinical purposes.

References

Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade. Science. 2018;359(6382):1350-1355. doi:10.1126/science.aar4060
Twomey JD, Zhang B. Cancer immunotherapy update: FDA-approved checkpoint inhibitors and companion diagnostics. AAPS J. 2021;23(2):39. doi:10.1208/s12248-021-00574-0
Liu X, Guo C, Tou F, et al. Association of PD-L1 expression status with the efficacy of PD-1/PD-L1 inhibitors and overall survival in solid tumours: a systematic review and meta-analysis. Int J Cancer. 2020;147(1):116-127. doi:10.1002/ijc.32744
BAVENCIO®. Prescribing information. EMD Serono Inc; 2022. Accessed June 26, 2023. https://www.emdserono.com/us-en/pi/bavencio-pi.pdf
IMFINZI®. Prescribing information. AstraZeneca Pharmaceuticals LP; 2022. Accessed June 26, 2023. http://www.azpicentral.com/pi.html?product=imfinzi
KEYTRUDA®. Prescribing information. Merck & Co Inc; 2023. Accessed June 26, 2023. https://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf
LIBTAYO®. Prescribing information. Regeneron Pharmaceuticals Inc; 2023. Accessed June 26, 2023. https://www.regeneron.com/downloads/libtayo_fpi.pdf
OPDIVO®. Prescribing information. Bristol-Meyers Squibb Company; 2023. Accessed June 26, 2023. https://packageinserts.bms.com/pi/pi_opdivo.pdf
TECENTRIQ®. Prescribing information. Genentech Inc; 2022. Accessed June 26, 2023. https://www.gene.com/download/pdf/tecentriq_prescribing.pdf
JEMPERLI. Prescribing information. GSK group of companies or its licensor; 2023. Accessed June 26, 2023. https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Jemperli/pdf/JEMPERLI-PI-MG.PDF
ZYNZYTM. Prescribing information. Incyte Corporation; 2023. Accessed June 26, 2023. https://www.zynyz.com/pdf/prescribing-information.pdf
PD-L1 IHC 22C3 pharmDx. Package insert. Dako North America Inc; 2022. Accessed June 26, 2023. https://www.agilent.com/cs/library/packageinsert/public/P03951E_23.pdf
PD-L1 IHC 28-8 pharmDx. Package insert. Dako North America Inc; 2020. Accessed June 26, 2023. https://www.agilent.com/cs/library/packageinsert/public/PD04163E_08.pdf
VENTANA PD-L1 (SP142) Assay. Package insert. Ventana Medical Systems Inc; 2020.
VENTANA PD-L1 (SP263) Assay. Package insert. Ventana Medical Systems Inc; 2022.
List of cleared or approved companion diagnostic devices (in vitro and imaging tools). U.S. Food and Drug Administration. Accessed July 18, 2023. https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools
Shah MA, Kennedy EB, Alarcon-Rozas AE, et al. Immunotherapy and targeted therapy for advanced gastroesophageal cancer: ASCO guideline. J Clin Oncol. 2023;41(7):1470-1491. doi:10.1200/jco.22.02331

Content reviewed 09/2023

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This Test Guide provides an overview of the use of tests for PD-L1 and other biomarkers involved in selection of PD-1/PD-L1 inhibitor therapy.

Test Guide List

PD-L1: Test Selection Guide

Test Guide

PD-L1

Test Selection Guide

Table 1. Summary of Testing Indications and Requirements With FDA-approved PD-L1 Clonesa

Clone
Disease	Therapy	Indications and PD-L1 testing requirements
PD-L1 IHC 22C3 pharmDx12
NSCLC	Keytruda® (pembrolizumab),6 see test code 93279 in Table 2 for test information	PD-L1 testing required (companion diagnostic) 1st-line treatment for PD-L1+ (TPS ≥1%) stage III (not eligible for resection or chemoradiation) or metastatic disease (no EGFR or ALK aberrations) Treatment for PD-L1+ (TPS ≥1%) metastatic disease with progression on or after platinum-based therapy (no EGFR or ALK aberrations, or with progression after treatment for EGFR or ALK aberrant disease) PD-L1 testing indicated but not required 1st-line treatment (combo) for metastatic nonsquamous disease (no EGFR or ALK aberrations) 1st-line treatment (combo) for metastatic squamous disease Treatment (adjuvant) for stage IB (tumor size ≥4 cm), II, or IIIA disease after resection and platinum-based chemotherapy
NSCLC	Libtayo® (cemiplimab),7 see test code 93279 in Table 2 for test information	PD-L1 testing required (companion diagnostic) 1st-line treatment for highly PD-L1+ (TPS ≥50%) advanced (not eligible for resection or chemoradiation) or metastatic disease (no EGFR, ALK, or ROS1 aberrations)
Cervical cancer	Keytruda® (pembrolizumab),6 see test code 36260 in Table 2 for test information	PD-L1 testing required (companion diagnostic) Treatment (combo) for PD-L1+ (CPS ≥1) persistent, recurrent, or metastatic disease Treatment for PD-L1+ (CPS ≥1) recurrent or metastatic disease with progression on or after chemotherapy
ESCC	Keytruda® (pembrolizumab),6 see test code 36260 in Table 2 for test information	PD-L1 testing required (companion diagnostic) Treatment for PD-L1+ (CPS ≥10) advanced or metastatic disease after ≥1 lines of therapy (not amenable for resection or chemoradiation) PD-L1 testing indicated but not required Treatment (combo) for advanced or metastatic disease (not amenable for resection or chemoradiation)
HNSCC	Keytruda® (pembrolizumab),6 see test code 36260 in Table 2 for test information	PD-L1 testing required (companion diagnostic) 1st-line treatment for PD-L1+ (CPS ≥1) metastatic or unresectable recurrent disease PD-L1 testing indicated but not required 1st-line treatment (combo) for metastatic or unresectable recurrent disease Treatment for metastatic or recurrent disease with progression on or after platinum-based therapy
TNBC	Keytruda® (pembrolizumab),6 see test code 36260 in Table 2 for test information	PD-L1 testing required (companion diagnostic) Treatment (combo) for PD-L1+ (CPS ≥10) locally recurrent unresectable or metastatic disease PD-L1 testing indicated but not required Treatment (combo, adjuvant) for high-risk early-stage disease after resection
Gastric/GEJ adenocarcinoma	Keytruda® (pembrolizumab),6 see test code 36260 in Table 2 for test information	PD-L1 testing indicated but not required 1st-line treatment (combo) for advanced unresectable or metastatic HER2+ disease 1st-line treatment (combo) for PD-L1+ (CPS ≥10) HER2-diseaseb
Ventana PD-L1 SP14214
NSCLC	Tecentriq® (atezolizumab),9 see test code 94480 in Table 2 for test information	PD-L1 testing required (companion diagnostic) 1st-line treatment for PD-L1+ (TC ≥50% or IC ≥10%) metastatic disease (no EGFR or ALK aberrations) PD-L1 testing indicated but not required 1st-line treatment (combo) for metastatic non-squamous disease (no EGFR or ALK aberrations) Treatment for metastatic disease with progression on or after platinum-based therapy (no EGFR or ALK aberrations, or with progression after treatment for EGFR- or ALK-aberrant disease)
PD-L1 IHC 28-8 pharmDx13
NSCLC	Opdivo® (nivolumab),8 see test code 93359 in Table 2 for test information	PD-L1 testing required (companion diagnostic) 1st-line treatment (combo) for PD-L1+ (expression ≥1%) metastatic disease (no EGFR or ALK aberrations) PD-L1 testing optional (complementary diagnostic) Treatment for non-squamous NSCLC PD-L1 testing indicated but not required Treatment (neoadjuvant and combo) for resectable (tumors ≥4 cm or node positive) disease 1st-line treatment (combo) for recurrent or metastatic disease (no EGFR or ALK aberrations) Treatment for metastatic disease with progression on or after platinum-based therapy (no EGFR or ALK aberrations, or with progression after treatment for EGFR- or ALK-aberrant disease)
HNSCC	Opdivo® (nivolumab),8 see test code 93793 in Table 2 for test information	PD-L1 testing optional (complementary diagnostic) Treatment for recurrent or metastatic disease with progression on or after platinum-based therapy
Urothelial carcinoma	Opdivo® (nivolumab),8 see test code 93793 in Table 2 for test information	PD-L1 testing optional (complementary diagnostic) Treatment for advanced or metastatic disease with progression on or after platinum-based therapy PD-L1 testing indicated but not required Treatment (adjuvant) after resection if high risk of recurrence
Ventana PD-L1 SP26315,c
NSCLC	Tecentriq® (atezolizumab)9	PD-L1 testing required (companion diagnostic) Treatment (adjuvant) for PD-L1+ (TC ≥1%) stage II to IIIA disease after resection and platinum-based therapy
NSCLC	Libtayo® (cemiplimab)7	PD-L1 testing indicated but not required 1st-line treatment (combo) for advanced (not eligible for resection or chemoradiation) or metastatic disease (no EGFR, ALK, or ROS1 aberrations)

CPS, combined positive score; ESCC, esophageal squamous-cell carcinoma; GEJ, gastroesophageal junction; HNSCC, head and neck squamous-cell carcinoma; IC, immune cells; IHC, immunohistochemistry; NSCLC, non–small-cell lung cancer; PD-L1, programmed death-ligand 1; TC, tumor cells; TNBC, triple-negative breast cancer; TPS, tumor proportion score.
a	This table is only intended as a summary for convenience. The appropriate drug prescribing information and test package insert should be consulted for further information on use and limitations of use.
b	The American Society of Clinical Oncology (ASCO) recommends testing PD-L1 expression for this indication.17
c	FDA-approved PD-L1 testing with clone SP263 for NSCLC is only available through PhenoPath. Contact Oncology Client Services at 1.866.894.6920 or refer to the PhenoPath test menu (http://phenopath.com/test-menu) for test information.

Table 2. Tests Available for Assessing PD-L1 Expression

Test code	Test name	Clinical use	Method and interpretation
PD-L1, clone 22C3 (Keytruda [pembrolizumab] and Libtayo [cemiplimab])
93279	PD-L1 Lung (Pembrolizumab or Cemiplimab), IHC	Identify patients with NSCLC who may be eligible for treatment with pembrolizumab or cemiplimaba	PD-L1 protein expression is determined using an IHC method (22C3). Results are based on TPS, which is the percentage of viable tumor cells showing partial or complete membrane staining. The specimen is considered PD-L1–positive if TPS is ≥1% (for pembrolizumab) or ≥50% (for cemiplimab).12
36260	PD-L1 Non-Lung (Pembrolizumab), IHC	Identify patients with non-NSCLC tumor typesb who may be eligible for treatment with pembrolizumaba	PD-L1 protein expression is determined using an IHC method (22C3). Results are based on CPS, which is the number of PD-L1–staining cells (for tumor cells, partial or complete membrane staining; for lymphocytes and macrophages, membrane and/or cytoplasmic staining) divided by the number of viable tumor cells, multiplied by 100. The specimen is considered PD-L1–positive if CPS is ≥1 (cervical cancer, HNSCC) or ≥10 (ESCC, TNBC).12
PD-L1, clone SP142 (Tecentriq [atezolizumab])
94480	PD-L1 Lung (Atezolizumab), IHC	Identify patients with NSCLC who may be eligible for treatment with atezolizumaba	PD-L1 protein expression is determined using an IHC method (SP142). Results are based on TC, which is the percentage of tumor cells showing partial or complete membrane staining, or IC, which is the percentage of tumor area covered by PD-L1–staining tumor-infiltrating immune cells. The specimen is considered PD-L1–positive if TC ≥50% or IC ≥10%.14
PD-L1, clone 28-8 (Opdivo [nivolumab])
93359	PD-L1 Lung (Nivolumab), IHC	Identify patients with NSCLC who may be eligible for treatment with nivolumab combination therapya Identify patients with non-squamous NSCLC who may have enhanced survival if treated with nivolumab	PD-L1 protein expression is determined using an IHC method (28-8). Results are based on % PD-L1 expression, which is the percentage of viable tumor cells showing partial or complete membrane staining. The specimen is considered PD-L1–positive if PD-L1 expression is ≥1%.13
93793	PD-L1 Non-Lung (Nivolumab), IHC	Identify patients with non-NSCLC tumor typesc who may have enhanced survival or response rate if treated with nivolumab	PD-L1 protein expression is determined using an IHC method (28-8). Results are based on % PD-L1 expression, which is the percentage of viable tumor cells showing partial or complete membrane staining. The specimen is considered PD-L1–positive if PD-L1 expression is ≥1% (HNSCC, urothelial carcinoma).13
PD-L1, generic
94007	PD-L1, IHC With Interpretationc	Detect PD-L1 expression in cancersd	PD-L1 protein expression is determined using an IHC method (SP263). Results are based on % TC, and % IC (when applicable).

CPS, combined positive score; ESCC, esophageal squamous-cell carcinoma; GEJ, gastroesophageal junction; HNSCC, head and neck squamous-cell carcinoma; IC, immune cells; IHC, immunohistochemistry; NSCLC, non–small-cell lung cancer; PD-L1, programmed death-ligand 1; TC, tumor cells; TNBC, triple-negative breast cancer; TPS, tumor proportion score.
a	Documentation of PD-L1 expression on tumor cells and/or tumor-infiltrating immune cells using an FDA-approved test is a prerequisite for treatment with the indicated therapy.
b	This test currently is applicable only to specific tumor types.
c	This test was developed and its analytical performance characteristics have been determined by Quest Diagnostics. It has not been cleared or approved by the US FDA. This assay has been validated pursuant to the CLIA regulations and is used for clinical purposes.
d	FDA-approved PD-L1 testing with clone SP263 for NSCLC is only available through PhenoPath. The specimen is considered PD-L1–positive if TC ≥50% for Libtayo (cemiplimab) or TC ≥1% for Tecentriq (atezolizumab). Contact Oncology Client Services at 1.866.894.6920 or refer to the PhenoPath test menu (http://phenopath.com/test-menu) for test information.

Table 3. Other Tests Available to Guide the Selection of PD-1/PD-L1–Inhibitor Therapy

Test code	Test name	Clinical use
MSI
14989	Microsatellite Instability (MSI)a	Identify patients with unresectable or metastatic solid tumors who may be eligible for treatment with PD-1/PD-L1 targeted therapy
dMMR
91332	Lynch Syndrome Tumor Panel, IHC with Interpretation Includes MLH1 (test code 70196), MSH2 (test code 70197), MSH6 (test code 16938), and PMS2 (test code 16997).	Identify patients with unresectable or metastatic solid tumors who may be eligible for treatment with PD-1/PD-L1 targeted therapy
TMB
12354	Tumor Mutation Burdena	Identify patients with unresectable or metastatic solid tumors who may be eligible for treatment with PD-1/PD-L1 targeted therapy

dMMR, deficient mismatch repair; IHC, immunohistochemistry; MSI, microsatellite instability; TMB, tumor mutational burden.
a	This test was developed and its analytical performance characteristics have been determined by Quest. It has not been cleared or approved by the US FDA. This assay has been validated pursuant to the CLIA regulations and is used for clinical purposes.

References

Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade. Science. 2018;359(6382):1350-1355. doi:10.1126/science.aar4060
Twomey JD, Zhang B. Cancer immunotherapy update: FDA-approved checkpoint inhibitors and companion diagnostics. AAPS J. 2021;23(2):39. doi:10.1208/s12248-021-00574-0
Liu X, Guo C, Tou F, et al. Association of PD-L1 expression status with the efficacy of PD-1/PD-L1 inhibitors and overall survival in solid tumours: a systematic review and meta-analysis. Int J Cancer. 2020;147(1):116-127. doi:10.1002/ijc.32744
BAVENCIO®. Prescribing information. EMD Serono Inc; 2022. Accessed June 26, 2023. https://www.emdserono.com/us-en/pi/bavencio-pi.pdf
IMFINZI®. Prescribing information. AstraZeneca Pharmaceuticals LP; 2022. Accessed June 26, 2023. http://www.azpicentral.com/pi.html?product=imfinzi
KEYTRUDA®. Prescribing information. Merck & Co Inc; 2023. Accessed June 26, 2023. https://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf
LIBTAYO®. Prescribing information. Regeneron Pharmaceuticals Inc; 2023. Accessed June 26, 2023. https://www.regeneron.com/downloads/libtayo_fpi.pdf
OPDIVO®. Prescribing information. Bristol-Meyers Squibb Company; 2023. Accessed June 26, 2023. https://packageinserts.bms.com/pi/pi_opdivo.pdf
TECENTRIQ®. Prescribing information. Genentech Inc; 2022. Accessed June 26, 2023. https://www.gene.com/download/pdf/tecentriq_prescribing.pdf
JEMPERLI. Prescribing information. GSK group of companies or its licensor; 2023. Accessed June 26, 2023. https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Jemperli/pdf/JEMPERLI-PI-MG.PDF
ZYNZYTM. Prescribing information. Incyte Corporation; 2023. Accessed June 26, 2023. https://www.zynyz.com/pdf/prescribing-information.pdf
PD-L1 IHC 22C3 pharmDx. Package insert. Dako North America Inc; 2022. Accessed June 26, 2023. https://www.agilent.com/cs/library/packageinsert/public/P03951E_23.pdf
PD-L1 IHC 28-8 pharmDx. Package insert. Dako North America Inc; 2020. Accessed June 26, 2023. https://www.agilent.com/cs/library/packageinsert/public/PD04163E_08.pdf
VENTANA PD-L1 (SP142) Assay. Package insert. Ventana Medical Systems Inc; 2020.
VENTANA PD-L1 (SP263) Assay. Package insert. Ventana Medical Systems Inc; 2022.
List of cleared or approved companion diagnostic devices (in vitro and imaging tools). U.S. Food and Drug Administration. Accessed July 18, 2023. https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools
Shah MA, Kennedy EB, Alarcon-Rozas AE, et al. Immunotherapy and targeted therapy for advanced gastroesophageal cancer: ASCO guideline. J Clin Oncol. 2023;41(7):1470-1491. doi:10.1200/jco.22.02331

Content reviewed 09/2023

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Test Code 12354

Tumor Mutation Burden

The Tumor Mutation Burden (TMB) assay is intended to be used as an aid in predicting response to immuno-oncology therapies among patients with advanced solid tumor malignancies. Higher somatic TMB has been associated with improved survival in patients receiving immune checkpoint inhibitor therapy across a wide variety of cancer types. The FDA has approved Pembrolizumab therapy as treatment for patients with metastatic solid tumors using TMB as a biomarker. Clinical trials may be available for pa

Test Code 94007

PD-L1, IHC with Interpretation

This PD-L1 qualitative assay is intended for use in the detection of PD-L1 expression in cancers. Immunotherapies targeting the PD-1/PD-L1 pathway have been reported to have durable anti-tumor effects in a subset of patients with solid tumors.

Test Code 93279

PD-L1 Lung (Pembrolizumab or Cemiplimab), IHC

The PD-L1 pharmaDx qualitative assay is intended for use in the detection of PD-L1 in formalin-fixed, paraffin-embedded (FFPE) non-small cell lung carcinoma (NSCLC). PD-L1 IHC 22C3 pharmDx is indicated as an aid in identifying NSCLC patients who may be eligible for treatment with KEYTRUDA (pembrolizumab) or LIBTAYO (cemiplimab).

Test Code 14989

Microsatellite Instability (MSI)

Patients with early onset and family history of colon cancers are suggestive of hereditary nonpolyposis colon cancer (hnpcc) syndrome. Microsatellite instability analysis on tumor tissue is recommended as a screening test to identify individuals eligible for germline mutation analysis or mismatch repair genes. Microsatellite instability analysis can also be used to identify adult and pediatric patients with unrespectable or metastatic solid tumors who have failed frontline therapy and who would

Test Code 36260

PD-L1 Non-Lung (Pembrolizumab), IHC

PD-L1 IHC 22C3 pharmDx is indicated as an aid in identifying patients for treatment with KEYTRUDA® (Pembrolizumab). This FDA approved test currently is applicable only to specific tumor types.

For non-FDA approved test indications or sample types, order 94007-PD-L1, IHC with Interpretation.

For other FDA approved primary tumors, please order the following:
For NSCLC order 93279-PD-L1 Lung (Pembrolizumab), IHC, 93359-PD-L1 Lung (Nivolumab), IHC or 94480-PD

Test Code 93359

PD-L1 Lung (Nivolumab), IHC

The PD-L1 IHC 28-8pharmaDx qualitative assay is intended for use in the detection of PD-L1 expression in formalin-fixed, paraffin embedded (FFPE) non-squamous non-small cell lung carcinoma (NSCLC). PD-L1 expression in non-squamous NSCLC may be associated with enhanced survival from OPDIVO (nivolumab).

Test Code 93793

PD-L1 Non-Lung (Nivolumab), IHC

PD-L1 IHC 28-8 pharmDx is indicated as an aid in identifying patients for treatment with OPDIVO® (Nivolumab). This FDA approved test currently is applicable only to specific tumor types.

For non-FDA approved test indications or sample types, order 94007-PD-L1, IHC

For other FDA approved primary tumors, please order the following:
For Pembrolizumab:
1. NSCLC, order 93279-PD-L1 Lung (Pembrolizumab), IHC
2. Non-NSCLC, orde

Test Code 91332

Lynch Syndrome Tumor Panel, IHC with Interpretation

Genetic defects in these four mismatch repair proteins underlie most cases of Lynch syndrome or hereditary non-polyposis colorectal carcinoma (HNPCC). This IHC panel looks for loss of expression of one or more of these proteins in cases of suspected HNPCC in tumor tissues from colorectal carcinomas, endometrial carcinomas, sebaceous adenoma/carcinoma or other adnexal tumors. If IHC results are abnormal, guidance is provided in the report on the recommended next step in the workup.

Test Code 94480

PD-L1 Lung (Atezolizumab), IHC

TECENTRIQ is the first FDA-approved anti-PD-L1 cancer immunotherapy which is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) who have disease progression during or following platinum- containing chemotherapy. Determining a patient's PD-L1 expression level can provide insight into the survival benefit that may be achieved from treatment with TECENTRIQ. PD-L1 expression in ≥50% tumor cells (TC) or ≥10% tumor-infiltrating immune cells (IC)

IG/Reference Manual

Test Guide List

This page is a complete list of Test Guides created by Quest Diagnostics.

Topic Brief

Non-Small Cell Lung Cancer (NSCLC): Laboratory Support of Diagnosis and Management

This Topic Brief discusses the critical role that laboratory testing plays in NSCLC, from diagnosis to disease management.

Clinical Focus

Cutaneous Melanoma: Laboratory Support of Diagnosis and Management

This Clinical Focus discusses the critical role that laboratory testing plays in cutaneous melanoma, from diagnosis to disease management.

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Reference ranges are provided as general guidance only. To interpret test results use the reference range in the laboratory report.

The tests listed by specialty and category are a select group of tests offered. For a complete list of Quest Diagnostics tests, please adjust the filter options chosen, or refer to our Directory of Services.

PD-L1: Test Selection Guide

PD-L1: Test Selection Guide

Test Guide

Test Guide

(9) Related Tests

(3) Related Guides