Fact sheets

Lung cancer

Why test PD-L1
in NSCLC?

Programmed cell death ligand-1 (PD-L1) testing is recommended in all non-small cell lung cancer (NSCLC) tumour samples. Further, anti-PD-L1 immunotherapy has been associated with clinical benefit in patients with NSCLC. This fact sheet explains the importance of PD-L1 testing in NSCLC and treatment decision implications.

To download this fact sheet, click here.

Tissue sampling for PD-L1
testing in lung cancer

In order to carry out PD-L1 testing, appropriate samples are required; the way in which these samples are obtained and processed can impact the success of PD-L1 testing. This fact sheet provides an overview of the different samples appropriate for PD-L1 testing in lung cancer.

To download this fact sheet, click here.

VENTANA PD-L1 SP263 assay microscope scoring aid

This fact sheet provides practical guidance for determining the percentage of tumour cells with positive staining for PD-L1 in NSCLC samples.

To download this fact sheet, click here.

Concordance of PD-L1 IHC
tests in NSCLC

Several immunohistochemistry (IHC) assays for detecting PD-L1 in NSCLC tumours are commercially available. This fact sheet describes the different PD-L1 IHC assays and the concordance between them.

To download this fact sheet, click here.

Bladder Cancer

Why test PD-L1 in
bladder cancer?

Despite recent advances in the treatment of bladder cancer, there is an unmet need for biomarker-driven therapies to improve patient prognosis. This fact sheet describes the importance of PD-L1 testing in bladder cancer tumours.

To download this fact sheet, click here.

Concordance of PD-L1 IHC tests
in urothelial carcinoma

Several IHC assays for detecting PD-L1 in bladder cancer tumours are commercially available. This fact sheet describes the different PD-L1 IHC assays and the concordance between them.

To download this fact sheet, click here.

Tissue sampling for PD-L1 testing in bladder cancer

High-quality tumour samples are needed for PD-L1 testing; correct preparation and processing is critical for ensuring the success and validity of PD-L1 testing by IHC. This fact sheet describes the pre- and post-analytical considerations for PD-L1 testing in bladder cancer tumours.

To download this fact sheet, click here.

VENTANA PD-L1 SP263 assay
microscope scoring aid

This fact sheet provides practical guidance for determining the percentage of tumour cells (TCs) or immune cells (ICs) with positive staining for PD-L1 in urothelial carcinoma (UC) samples.

To download this fact sheet, click here.

PD-L1 scoring algorithm
in bladder cancer

Each PD-L1 IHC assay is associated with a specific algorithm and cut-off to define PD-L1 expression. This fact sheet describes the different PD-L1 scoring algorithms used in bladder cancer.

To download this fact sheet, click here.

Pan-cancer

PD-L1
e-trainer tool

AstraZeneca have partnered with Targos to provide an interactive, multi-assay training tool for PD-L1 stain interpretation. Pathologists can use the PD-L1 e-trainer to practice and improve their sample interpretation. A sample of the e-trainer tool is available on the Training page. This fact sheet provides an overview of the PD-L1 e-trainer tool.

To download this fact sheet, click here.

Back to top

 Videos

The role of PD-L1 testing for immunotherapy

The potential interchangeability of validated PD-L1 assays

The concordance of PD-L1 assays in NSCLC

The validation of PD-L1 LDTs

The use of cytology samples for PD-L1 testing

The issue of borderline PD-L1 expression interpretation

Back to top

Guidelines

Canadian Association of Pathologists (CAP)-Association Canadienne Des Pathologistes (ACP)

The CAP-ACP jointly proposed a guideline on PD-L1 biomarker testing for patient selection in immuno-oncology.

To view the CAP-ACP guidelines, click here.

International Association for the Study of Lung Cancer (IASLC)

The IASLC provided a perspective for PD-L1 testing in lung cancer, including considerations on pre-analytical, analytical and post-analytical aspects of PD-L1 IHC.

To view the IASLC perspective on PD-L1 testing in lung cancer, click here.

National Comprehensive Cancer Network (NCCN)

The NCCN Clinical Practice Guidelines for NSCLC is a series of recommendations for the risk assessment, evaluation and treatment of patients with the disease. There is also some guidance for PD-L1 testing.

To view the latest NCCN Clinical Practice Guidelines for NSCLC, click here.

Society for Immunotherapy of Cancer (SITC)

The SITC convened an expert Task Force to develop a consensus statement on immunotherapy for the treatment of NSCLC. Within the statement, there are recommendations for PD-L1 testing.

To view the SITC consensus statement, click here.

Back to top

Key Publications

Guidelines

CAP-ACP:

Cheung CC, Barnes P, Bigras G, et al. Fit-for-purpose PD-L1 biomarker testing for patient selection in immuno-oncology: guidelines for clinical laboratories from the Canadian Association of Pathologists-Association Canadienne Des Pathologistes (CAP-ACP).Appl Immunohistochem Mol Morphol 2019;27:699–714. doi:10.1097/PAI.0000000000000800

 

 

NCCN:

NCCN. NCCN Clinical Practice Guidelines in Oncology Non-Small Cell Lung Cancer Version 3.2020. Available at: https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf (accessed 17 February 2020)

IASLC:

Lantuejoul S, Sound-Tsao M, Cooper WA, et al. PD-L1 testing
for lung cancer in 2019: perspective from the IASLC Pathology Committee [published online ahead of print, 2019 Dec 20]. J Thorac Oncol2019;S1556-0864(19)33847-X. doi:10.1016/j.jtho.2019.12.107

 

 

 

SITC:

Brahmer JR, Govindan R, Anders RA, et al. The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of non-small cell lung cancer (NSCLC).J Immunother Cancer2018;6:75. doi:10.1186/s40425-018-0382-2

Cheung CC, Barnes P, Bigras G, et al. Fit-for-purpose PD-L1 biomarker testing for patient selection in immuno-oncology: guidelines for clinical laboratories from the Canadian Association of Pathologists-Association Canadienne Des Pathologistes (CAP-ACP).Appl Immunohistochem Mol Morphol 2019;27:699–714. doi:10.1097/PAI.0000000000000800

Lantuejoul S, Sound-Tsao M, Cooper WA, et al. PD-L1 testing for lung cancer in 2019: perspective from the IASLC Pathology Committee [published online ahead of print, 2019 Dec 20]. J Thorac Oncol2019;S1556-0864(19)33847-X. doi:10.1016/j.jtho.2019.12.107

NCCN. NCCN Clinical Practice Guidelines in Oncology Non-Small Cell Lung Cancer Version 3.2020. Available at: https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf (accessed 17 February 2020)

Brahmer JR, Govindan R, Anders RA, et al. The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of non-small cell lung cancer (NSCLC). J Immunother Cancer2018;6:75. doi:10.1186/s40425-018-0382-2

Back to top

Frequently asked questions

  1. What samples can be used for PD-L1 testing?

  • Routinely processed, formalin-fixed paraffin-embedded (FFPE) tumour biopsy or resection samples are suitable for use.1 Both tumour biopsy samples that were acquired at diagnosis, FFPE processed and archived and newly acquired tumour biopsy samples that undergo FFPE processing may be used2, 3
  • The VENTANA SP263 assay is also validated for use with NSCLC FFPE fine-needle aspiration (FNA) cell blocks for the assessment of TC PD-L1 expression1
  • Biopsy samples from primary and metastatic lesions are suitable3

  1. Can cytology samples be used?

  • The VENTANA SP263 assay is the only commercially-available PD-L1 IHC assay that is validated for use with NSCLC FFPE FNA cell blocks1
    • Other cytology samples such as smears obtained from bronchoscopy brushings, washes, lavages or pleural effusions or liquid-spin preparations are currently not validated for use with the VENTANA SP263 assay1
  • The VENTANA SP142, PD-L1 IHC 22C3 pharmDx and PD-L1 IHC 28-8 pharmDx assays are not fully validated for use with cytology samples4-6

  1. Can I use blood-based samples?

  • Blood-based biopsies are not currently suitable for PD-L1 testing

  1. Can re-biopsy samples be used?

  • Yes, if no other suitable sample is available

  1. What are the minimum sample requirements?

  • Tissue sections cut from the tumour biopsy for IHC staining should be approximately 4–6 μm in thickness and have an adequate number of viable tumour cells (≥100)1, 7

  1. Will I get a different PD-L1 test result depending on the location of the sample (e.g. primary tumour vs. metastatic)?

  • The prevalence of PD-L1 expression is similar in primary and metastatic lesions, and samples from either site can be used for determination of PD-L1 expression3
  • Results from the ATLANTIC study have demonstrated similarity in the prevalence of high PD-L1 expression levels in primary and metastatic lesions, supporting the use of samples obtained from either location3

  1. Which cells (ICs vs. TCs) should be assessed? Does this differ by indication?

  • The cell type being assessed and the cut-offs used to categorise PD-L1 expression differ depending on the immunotherapy option being considered8-10

  1. What is the rationale behind including TCs and ICs in a scoring algorithm?

  • In normal tissue, PD-L1 is expressed on a variety of cells including a subset of T cells, B cells, dendritic cells, macrophages, mesenchymal stem cells, and bone marrow-derived mast cells, as well as various non-hematopoietic cells7
  • PD-L1 is also expressed in a broad range of carcinomas and other cancers, providing the tumour with protection from activated T cells and immune elimination7
  • The inclusion of both TCs and ICs (as appropriate, depending on the indication) into a scoring algorithm provides an assessment of PD-L1 expression levels and identifies patients most likely to respond to treatment11

  1. What is the rationale behind scoring TCs and ICs in UC?

  • Scoring TCs and ICs in UC is dependent on the PD-L1 test and treatment being considered
  • In a clinical study examining tumour biopsy samples from patients with UC, it was not possible to clearly separate responders from non-responders using PD-L1 expression on TCs only or ICs only. However, when PD-L1 status was defined on the basis of its expression on either TCs or ICs, it was possible to differentiate between responders and non-responders. A correlation with response to treatment was also observed on combining TC and IC scoring11

  1. How do we reconcile the differences among the different assays with regards to PD-L1 cut-offs?

  • Results from concordance studies in biopsies taken from patients with NSCLC, head and neck squamous cell carcinoma (HNSCC) and UC have demonstrated strong overall percentage agreement in tumour PD-L1 staining at different cut-offs between three commercially available PD-L1 assays (PD-L1 IHC 22C3, PD-L1 IHC 28-8 and VENTANA SP263).12-19In principle, if concordance is sufficiently demonstrated, it may be possible to use some commercially available PD-L1 staining tests interchangeably; however, further research in specific tumour types is needed to confirm this.

Back to top

References

 

 

  1. Roche. VENTANA PD-L1 (SP263) Assay package insert. 2020. Available from: https://pim-eservices.roche.com/eLD/api/downloads/4b0ce998-2fb6-ea11-fc90-005056a71a5d?countryIsoCode=gb. Accessed: 5 October 2020
  2. Herbst RS, Baas P, Kim D-W, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet 2016;387:1540–1550
  3. Midha A, Sharpe A, Scott M, et al. PD-L1 expression in advanced NSCLC: primary lesions versus metastatic sites and impact of sample age. J Clin Oncol 2016;34:3025
  4. Roche. VENTANA PD-L1 (SP142) Assay package insert (FDA). 2016. Available from: https://www.accessdata.fda.gov/cdrh_docs/pdf16/p160006c.pdf. Accessed: 15 May 2020
  5. Dako. PD-L1 IHC 22C3 pharmDx package insert (FDA). 2018. Available from: https://www.accessdata.fda.gov/cdrh_docs/pdf15/P150013S011C.pdf. Accessed: 15 May 2020
  6. Dako. PD-L1 IHC 28-8 pharmDx package insert (FDA). 2017. Available from: https://www.accessdata.fda.gov/cdrh_docs/pdf15/P150025S003C.pdf. Accessed: 15 May 2020
  7. Rebelatto MC, Midha A, Mistry A, et al. Development of a programmed cell death ligand-1 immunohistochemical assay validated for analysis of non-small cell lung cancer and head and neck squamous cell carcinoma. Diagn Pathol 2016;11:95
  8. Roche. VENTANA PD-L1 (SP263) Assay (CE IVD). 2020. Available from: https://diagnostics.roche.com/global/en/products/tests/ventana-pd-l1-_sp263-assay2.html. Accessed: 15 May 2020
  9. Barlesi F, Vansteenkiste J, Spigel D, et al. Avelumab versus docetaxel in patients with platinum-treated advanced non-small-cell lung cancer (JAVELIN Lung 200): an open-label, randomised, phase 3 study. Lancet Oncol 2018;19:1468–1479
  10. Antonia SJ, Villegas A, Daniel D, et al. Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC. N Engl J Med 2018;379:2342–2350
  1. 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;34:3119–3125
  2. Ratcliffe MJ, Sharpe A, Midha A, et al. Agreement between programmed cell death ligand-1 diagnostic assays across multiple protein expression cutoffs in non-small cell lung cancer. Clin Cancer Res 2017;23:3585–3591
  3. Tsao MS, Kerr KM, Kockx M, et al. PD-L1 immunohistochemistry comparability study in real-life clinical samples: results of blueprint phase 2 project. J Thorac Oncol 2018;13:1302–1311
  4. Hirsch FR, McElhinny A, Stanforth D, et al. PD-L1 immunohistochemistry assays for lung cancer: results from phase 1 of the blueprint PD-L1 IHC assay comparison project. J Thorac Oncol 2017;12:208–222
  5. Adam J, Le Stang N, Rouquette I, et al. Multicenter harmonization study for PD-L1 IHC testing in non-small-cell lung cancer. Ann Oncol 2018;29:953–958
  6. Rimm DL, Han G, Taube JM, et al. A prospective, multi-institutional, pathologist-based assessment of 4 immunohistochemistry assays for PD-L1 expression in non-small cell lung cancer. JAMA Oncol 2017;3:1051–1058
  7. Zajac M, Scott M, Ratcliffe M, et al. Concordance among four commercially available, validated programmed cell death ligand-1 assays in urothelial carcinoma. Diagn Pathol 2019;14:99
  8. Ratcliffe MJ, Sharpe A, Midha A, et al. Abstract LB-094: A comparative study of PD-L1 diagnostic assays and the classification of patients as PD-L1 positive and PD-L1 negative. Cancer Research 2016;76:LB-094
  9. Ratcliffe MJ, Sharpe A, Rebelatto M, et al. A comparative study of PD-L1 diagnostic assays in squamous cell carcinoma of the head and neck (SCCHN). Ann Oncol 2016;27:vi330
Back to top