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How to test

PD-L1 expression in tumour samples is quantified using immunohistochemistry-based assays1–4

Key requirements for testing are an appropriate tumour sample and a validated PD-L1 test

  • Appropriate tumour samples
    • Formalin-fixed, paraffin-embedded tumour biopsy samples containing an adequate number of tumour cells can be used for PD-L1 testing1–4
    • Analysis of NSCLC samples suggests that both newly acquired and archival tumour tissue provides informative results regarding PD-L1 expression levels5,6
    • PD-L1 testing in urothelial bladder cancer samples supports the use of tissue obtained from primary and metastatic lesions for determination of PD-L1 expression levels3,7
  • PD-L1 tests
    • Multiple PD-L1 tests are in development/approved to assess PD-L1 expression using automated immunohistochemistry (PD-L1 diagnostics) – see Table below for a summary of these tests. To date, one PD-L1 test is approved as a complementary diagnostic for bladder cancer (Ventana PD-L1 [SP142] Assay)
Test Dako 22C31 Dako 28-82 Ventana SP1423,8 Ventana SP2634

Instrument/platform used for IHC processing

Dako Autostainer
Link 48

Dako Autostainer
Link 48

Ventana BenchMark
Ultra

Ventana BenchMark
Ultra

PD-L1 monoclonal antibody

22C3

28-8

SP142

SP263

Diagnostic type

IVD companion diagnostic in NSCLC

IVD complementary diagnostic in non-squamous NSCLC and melanoma

IVD complementary diagnostic in bladder cancer3 and NSCLC8

IVD, CE-IVD Class I and indicated as an aid in NSCLC

Test

Instrument/platform used for IHC processing

PD-L1 monoclonal antibody

Diagnostic type

Dako 22C31

Dako Autostainer
Link 48

22C3

IVD companion diagnostic in NSCLC

Dako 28-82

Dako Autostainer
Link 48

28-8

IVD complementary diagnostic in non-squamous NSCLC and melanoma

Ventana SP1423,8

Ventana BenchMark
Ultra

SP142

IVD complementary diagnostic in bladder cancer3 and NSCLC8

Ventana SP2634

Ventana BenchMark
Ultra

SP263

IVD, CE-IVD Class I and indicated as an aid in NSCLC

    • Companion diagnostics are required for the safe and effective use of a corresponding therapeutic product in a targeted patient population9
    • Complementary diagnostics are not essential for determining who should receive a drug; they provide information about how a drug might be used and how well a patient might respond10
  • PD-L1 expression may be present at varying frequency and intensity within the membrane and cytoplasm of tumour cells and infiltrating immune cells1–3,5
Representation of PD-L1 expression localised in a tumour sample

PD-L1 expression localised in a tumour sample

  • Each PD-L1 test has a defined PD-L1 cutoff for tumour samples biopsied from patients with bladder cancer. This is a percentage of PD-L1 expression that separates out those patients who do, and do not, respond to a PD-1/PD-L1-targeted agent,11-16 (determined by analysis of clinical efficacy data and PD-L1 expression levels in samples obtained from patients in clinical studies)
  • A scoring algorithm based on the PD-L1 cutoff point provides a set of rules for a pathologist to classify a patient’s tumour sample as having high, low, or no PD-L1 expression11-16
    • It is important that pathologists are trained in application of the scoring algorithm for consistency of patient classification16

CE, Conformité Européene; IVD, in vitro diagnostic; NSCLC, non-small cell lung cancer; PD-L1, programmed cell death ligand-1

REFERENCES

  1. Dako PD-L1 IHC 22C3 pharmDx. Last accessed December 2016
    http://www.accessdata.fda.gov/cdrh_docs/pdf15/P150013c.pdf
  2. Dako PD-L1 IHC 28-8 pharmDx. Last accessed December 2016
    http://www.accessdata.fda.gov/cdrh_docs/pdf15/P150025c.pdf
  3. VENTANA PD-L1 (SP142) Assay. Last accessed December 2016
    http://www.accessdata.fda.gov/cdrh_docs/pdf16/P160002c.pdf
  4. VENTANA PD-L1 (SP263) Assay. Last accessed December 2016
    http://www.ventana.com/product/1815?type=2324
  5. Herbst RS, et al. Lancet 2016;387:1540–50
  6. Midha A, et al. Poster presented at ASCO 2016 (Abstract 3025)
  7. Zajac M, et al. Poster Presentation at AACR 2017 (Abstract 656)
  8. Press release. Roche announces FDA approval for VENTANA PD-L1 (SP142) Assay to support immunotherapy treatment decisions in lung cancer. Last accessed December 2016
    http://www.ventana.com/roche-receives-fda-approval-for-pd-l1-assay-for-nsclc+
  9. US FDA. In Vitro Companion Diagnostic Devices. Guidance for Industry and FDA Staff; 2014. Last accessed December 2016
    http://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm262327.pdf
  10. ASCPT 2016. Last accessed December 2016
    http://www.ascpt.org/CTS/Blog-Translational-Bytes/ArtMID/121480/ArticleID/27/New-Drug-Rounds-Complementary-Diagnostics-%E2%80%93-Will-You-Test
  11. Sharma P, et al. Oral presentation at ASCO 2016 (abstract 4501)
  12. Rosenberg JE, et al. Lancet 2016;387:1909–20
  13. Powles T, et al. Nature 2014;515:558–62
  14. Apolo AB, et al. Poster presented at ASCO 2016 (abstract 4514)
  15. Massard C, et al. J Clin Oncol 2016;34:3119–25
  16. Cree IA, et al. Histopathology 2016;69:177–86

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