PD-L1 High Expression

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Associated Diseases

Overview

Variant Type

High Expression

Biomarker-Directed Therapies

View Therapies for PD-L1 High Expression

PD-L1 High Expression is a predictive biomarker for use of pembrolizumab, atezolizumab, cemiplimab, ipilimumab, nab-paclitaxel, and nivolumab in patients.

Of the therapies with PD-L1 High Expression as a predictive biomarker, 6 are FDA-approved and 4 have NCCN guidelines in at least one clinical setting.

Non-small cell lung carcinoma and breast carcinoma have the most therapies targeted against PD-L1 High Expression or its related pathways [5].

Atezolizumab +

Non-Small Cell Lung Carcinoma -

Biomarker Criteria:

Sample must match all of the following:

Sample must match one or more of the following:

PD-L1 Expression, PD-L1 High Expression

Sample must not match any of the following:

ALK Fusion, EGFR T790M

EGFR Sensitizing Mutations

Predicted Response: Primary Sensitivity

Clinical Setting(s): Metastatic (FDA, NCCN)

Note: Approved for the first-line treatment of adult patients with metastatic NSCLC with high PD-L1 expression (PD-L1 stained ≥ 50% of tumor cells [TC ≥ 50%] or PD-L1 stained tumor-infiltrating immune cells [IC] covering ≥ 10% of the tumor area [IC ≥ 10%]), with no EGFR or ALK alterations.

Biomarker Criteria: Sample must match all of the following: Sample must match one or more of the following: PD-L1 Expression, PD-L1 High Expression Sample must not match any of the following: ALK Fusion, EGFR T790M EGFR Sensitizing Mutations	Predicted Response: Primary Sensitivity
	Clinical Setting(s): Metastatic (FDA, NCCN)
	Note: Approved for the first-line treatment of adult patients with metastatic NSCLC with high PD-L1 expression (PD-L1 stained ≥ 50% of tumor cells [TC ≥ 50%] or PD-L1 stained tumor-infiltrating immune cells [IC] covering ≥ 10% of the tumor area [IC ≥ 10%]), with no EGFR or ALK alterations.

Cemiplimab +

Non-Small Cell Lung Carcinoma -

Biomarker Criteria:

Sample must match all of the following:

Sample must match one or more of the following:

PD-L1 High Expression

Sample must not match any of the following:

ALK Fusion, EGFR T790M, ROS1 Fusion

EGFR Sensitizing Mutations

Predicted Response: Primary Sensitivity

Clinical Setting(s): Metastatic (FDA, NCCN)

Note: For high expression of PD-L1 (Tumor Proportion Score >= 50%, clone 22C3) in the absence of EGFR/ALK/ROS1 (FDA/NCCN) and RET/BRAF V600E/MET Exon 14 Skipping (NCCN) mutations: recommended as a single agent for first-line therapy.

Biomarker Criteria: Sample must match all of the following: Sample must match one or more of the following: PD-L1 High Expression Sample must not match any of the following: ALK Fusion, EGFR T790M, ROS1 Fusion EGFR Sensitizing Mutations	Predicted Response: Primary Sensitivity
	Clinical Setting(s): Metastatic (FDA, NCCN)
	Note: For high expression of PD-L1 (Tumor Proportion Score >= 50%, clone 22C3) in the absence of EGFR/ALK/ROS1 (FDA/NCCN) and RET/BRAF V600E/MET Exon 14 Skipping (NCCN) mutations: recommended as a single agent for first-line therapy.

Pembrolizumab +

Non-Small Cell Lung Carcinoma -

Biomarker Criteria:

Sample must match all of the following:

PD-L1 High Expression

Predicted Response: Primary Sensitivity

Clinical Setting(s): Metastatic (FDA, NCCN, ASCO)

Note: For high expression of PD-L1 (Tumor Proportion Score >= 50%, clone 22C3) in the absence of EGFR & ALK (FDA/NCCN) and ROS1, RET, BRAF V600E, and MET Exon 14 Skipping (NCCN) mutations: recommended as a single agent for first-line therapy, or as subsequent line with disease progression during or following appropriate systemic chemotherapy.

Biomarker Criteria: Sample must match all of the following: PD-L1 High Expression	Predicted Response: Primary Sensitivity
	Clinical Setting(s): Metastatic (FDA, NCCN, ASCO)
	Note: For high expression of PD-L1 (Tumor Proportion Score >= 50%, clone 22C3) in the absence of EGFR & ALK (FDA/NCCN) and ROS1, RET, BRAF V600E, and MET Exon 14 Skipping (NCCN) mutations: recommended as a single agent for first-line therapy, or as subsequent line with disease progression during or following appropriate systemic chemotherapy.

Biomarker Criteria:

Sample must match all of the following:

Sample must match one or more of the following:

PD-L1 High Expression, PD-L1 Low Expression

Sample must match one or more of the following:

ALK Fusion, EGFR A763_Y764insFQEA, EGFR Exon 19 Deletion, EGFR Exon 19 Insertion, EGFR G719A, EGFR G719C, EGFR G719S, EGFR L858R, EGFR L861Q, EGFR S768I, EGFR T790M

Predicted Response: Primary Sensitivity

Clinical Setting(s): Metastatic (FDA)

Note: For PD-L1 expressing tumors (Tumor Proportion Score >=1%, clone 22C3) with an EGFR or ALK alteration: FDA-approved as subsequent line of therapy following targeted therapy. However, per NCCN, data in the second-line setting suggest that subsequent pembrolizumab monotherapy is less effective in tumors with an EGFR mutation or ALK rearrangement.

Biomarker Criteria: Sample must match all of the following: Sample must match one or more of the following: PD-L1 High Expression, PD-L1 Low Expression Sample must match one or more of the following: ALK Fusion, EGFR A763_Y764insFQEA, EGFR Exon 19 Deletion, EGFR Exon 19 Insertion, EGFR G719A, EGFR G719C, EGFR G719S, EGFR L858R, EGFR L861Q, EGFR S768I, EGFR T790M	Predicted Response: Primary Sensitivity
	Clinical Setting(s): Metastatic (FDA)
	Note: For PD-L1 expressing tumors (Tumor Proportion Score >=1%, clone 22C3) with an EGFR or ALK alteration: FDA-approved as subsequent line of therapy following targeted therapy. However, per NCCN, data in the second-line setting suggest that subsequent pembrolizumab monotherapy is less effective in tumors with an EGFR mutation or ALK rearrangement.

Biomarker Criteria:

Sample must match all of the following:

Sample must match one or more of the following:

PD-L1 High Expression, PD-L1 Low Expression

Sample must match one or more of the following:

BRAF V600E, RET Fusion, ROS1 Fusion, MET Exon 14 Skipping

Predicted Response: Primary Sensitivity

Clinical Setting(s): Metastatic (FDA, NCCN)

Note: For PD-L1 expressing tumors (Tumor Proportion Score >=1%, clone 22C3) with a ROS1, RET, BRAF V600E, or MET Exon 14 Skipping alteration: approved as a single agent for first- or subsequent-line therapy. However, per NCCN, targeted therapy for the oncogenic driver should take precedence over an immune checkpoint inhibitor.

Biomarker Criteria: Sample must match all of the following: Sample must match one or more of the following: PD-L1 High Expression, PD-L1 Low Expression Sample must match one or more of the following: BRAF V600E, RET Fusion, ROS1 Fusion, MET Exon 14 Skipping	Predicted Response: Primary Sensitivity
	Clinical Setting(s): Metastatic (FDA, NCCN)
	Note: For PD-L1 expressing tumors (Tumor Proportion Score >=1%, clone 22C3) with a ROS1, RET, BRAF V600E, or MET Exon 14 Skipping alteration: approved as a single agent for first- or subsequent-line therapy. However, per NCCN, targeted therapy for the oncogenic driver should take precedence over an immune checkpoint inhibitor.

Biomarker Criteria:

Sample must match one or more of the following:

PD-L1 High Expression, PD-L1 Low Expression

Predicted Response: Primary Sensitivity

Clinical Setting(s): Second Line of Therapy (NICE, SMC)

Note: Pembrolizumab is indicated as subsequent therapy for patients with NSCLC expressing CD274 (programmed death ligand 1 (PD-L1)), and whose disease has progressed on or after platinum-containing chemotherapy. An improved overall response rate was observed in CD274 (PD-L1) positive tumors.

Biomarker Criteria: Sample must match one or more of the following: PD-L1 High Expression, PD-L1 Low Expression	Predicted Response: Primary Sensitivity
	Clinical Setting(s): Second Line of Therapy (NICE, SMC)
	Note: Pembrolizumab is indicated as subsequent therapy for patients with NSCLC expressing CD274 (programmed death ligand 1 (PD-L1)), and whose disease has progressed on or after platinum-containing chemotherapy. An improved overall response rate was observed in CD274 (PD-L1) positive tumors.

Atezolizumab + Nab-Paclitaxel +

Breast Carcinoma -

Biomarker Criteria:

Sample must match all of the following:

Triple-Negative Breast Cancer Alterations

Sample must match one or more of the following:

PD-L1 Expression, PD-L1 High Expression, PD-L1 Low Expression

Predicted Response: Primary Sensitivity

Clinical Setting(s): Metastatic (FDA, NCCN)

Note: Indicated for adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1 (PD-L1 stained tumor-infiltrating immune cells [IC] of any intensity covering ≥ 1% of the tumor area.

Biomarker Criteria: Sample must match all of the following: Sample must match all of the following: Triple-Negative Breast Cancer Alterations Sample must match one or more of the following: PD-L1 Expression, PD-L1 High Expression, PD-L1 Low Expression	Predicted Response: Primary Sensitivity
	Clinical Setting(s): Metastatic (FDA, NCCN)
	Note: Indicated for adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1 (PD-L1 stained tumor-infiltrating immune cells [IC] of any intensity covering ≥ 1% of the tumor area.

Ipilimumab + Nivolumab +

Non-Small Cell Lung Carcinoma -

Biomarker Criteria:

Sample must match all of the following:

Sample must not match any of the following:

ALK Fusion, EGFR T790M

EGFR Sensitizing Mutations

Sample must match one or more of the following:

PD-L1 Expression, PD-L1 High Expression, PD-L1 Low Expression

Predicted Response: Primary Sensitivity

Clinical Setting(s): Metastatic (FDA)

Note: Approved as first-line treatment for patients with metastatic NSCLC whose tumors express PD-L1(≥1%), with no EGFR or ALK genomic tumor aberrations.

Biomarker Criteria: Sample must match all of the following: Sample must not match any of the following: ALK Fusion, EGFR T790M EGFR Sensitizing Mutations Sample must match one or more of the following: PD-L1 Expression, PD-L1 High Expression, PD-L1 Low Expression	Predicted Response: Primary Sensitivity
	Clinical Setting(s): Metastatic (FDA)
	Note: Approved as first-line treatment for patients with metastatic NSCLC whose tumors express PD-L1(≥1%), with no EGFR or ALK genomic tumor aberrations.

Clinical Trials

View Clinical Trials for PD-L1 High Expression

Significance of PD-L1 High Expression in Diseases

Non-Small Cell Lung Carcinoma +

Breast Carcinoma +

Malignant Solid Tumor +

Adenocarcinoma Of The Gastroesophageal Junction +

Gastric Adenocarcinoma +

Urothelial Carcinoma +

Head And Neck Squamous Cell Carcinoma +

Melanoma +

Squamous Cell Lung Carcinoma +

Non-Squamous Non-Small Cell Lung Carcinoma +

Bladder Carcinoma +

Colorectal Carcinoma +

Ovarian Carcinoma +

Renal Cell Carcinoma +

Alveolar Rhabdomyosarcoma +

Atypical Teratoid/Rhabdoid Tumor +

Bladder Urothelial Carcinoma +

Breast Adenocarcinoma +

Cervical Adenocarcinoma +

Cervical Adenosquamous Carcinoma +

Cervical Carcinoma +

Cervical Squamous Cell Carcinoma +

Childhood Central Nervous System Embryonal Carcinoma +

Clear Cell Renal Cell Carcinoma +

Cutaneous Melanoma +

Desmoplastic Small Round Cell Tumor +

Diffuse Intrinsic Pontine Glioma +

Diffuse Large B-Cell Lymphoma +

Embryonal Rhabdomyosarcoma +

Embryonal Tumor With Multilayered Rosettes, C19MC-Altered +

Endometrial Carcinoma +

Ependymoma +

Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor Of Bone +

Fallopian Tube Carcinoma +

Follicular Lymphoma +

Gastric Carcinoma +

Glioblastoma +

High Grade Ovarian Serous Adenocarcinoma +

Hodgkin Lymphoma +

Hypopharyngeal Squamous Cell Carcinoma +

Infiltrating Bladder Urothelial Carcinoma +

Infiltrating Renal Pelvis And Ureter Urothelial Carcinoma +

Laryngeal Squamous Cell Carcinoma +

Liver And Intrahepatic Bile Duct Carcinoma +

Lymphoma +

Malignant Glioma +

Malignant Mesothelioma +

Mediastinal Large B-Cell Lymphoma +

Medulloblastoma +

Mucosal Melanoma +

Multiple Myeloma +

Myelodysplastic Syndromes +

Neuroblastoma +

Non-Hodgkin Lymphoma +

Oral Cavity Squamous Cell Carcinoma +

Oropharyngeal Squamous Cell Carcinoma +

Ovarian Endometrioid Adenocarcinoma +

Pancreatic Ductal Adenocarcinoma +

Primary Peritoneal Carcinoma +

Prostate Adenocarcinoma +

Renal Pelvis Urothelial Carcinoma +

Rhabdoid Tumor +

Small Cell Lung Carcinoma +

Synovial Sarcoma +

Ureter Urothelial Carcinoma +

Urethral Urothelial Carcinoma +

Wilms Tumor +

References

1. Hart R and Prlic A. Universal Transcript Archive Repository. Version uta_20180821. San Francisco CA: Github;2015. https://github.com/biocommons/uta

2. The UniProt Consortium. UniProt: a worldwide hub of protein knowledge. Nucleic Acids Research. 2019;47:D506-D515.

3. Liu X, Wu C, Li C, and Boerwinkle E. dbNSFP v3.0: A one-stop database of functional predictions and annotations for human nonsynonymous and splice site SNVs. Human Mutation. 2015;37:235-241. 
Liu X, Jian X, and Boerwinkle E. dbNSFP: A lightweight database of human nonsynonymous SNPs and their functional predictions. Human Mutation. 2011;32:894-899.

4. The AACR Project GENIE Consortium. AACR Project GENIE: powering precision medicine through an international consortium. Cancer Discovery. 2017;7(8):818-831. Dataset Version 8. This dataset does not represent the totality of the genetic landscape; see paper for more information.

5. All assertions and clinical trial landscape data are curated from primary sources. You can read more about the curation process here.

Biomarkers /

Back to Biomarkers List

Associated Diseases

Overview

Biomarker-Directed Therapies

Clinical Trials

Significance of PD-L1 High Expression in Diseases

References

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