Integrazione di PD-L1 nel laboratorio di Anatomia Patologica

PDL1-Mechanism

Restifo NP et al : Nat Rev Cancer. 2016 Feb;16(2):121-6.

Adaptive vs Innate

Restifo NP et al : Nat Rev Cancer. 2016 Feb;16(2):121-6.

PDL1-CD8-Mutational load

Lung Cancer Subtypes

Non-Small Cell(65-85%)

Small Cell(15-35%)

No Driver Mutation (80%)

Oncogenic Driver Mutation (20%)

Adenocarcinoma (50-70%)

Large Cell(10-30%)

Nonsquamous(60-80%)

Squamous(20-40%)

ALK (2-5%)

EGFr (15-18%)

Lung Cancer

PD-L1

A Biomarker Is Defined As:

European Medicines Agency:• “Biomarkers are tests that can be used to follow body processes and

diseases in humans and animals. They can be used to predict how a patient will respond to a medicine or whether they have, or are likely to develop, a certain disease”2

1. FDA Guidance for Industry. www.fda.gov. Accessed March 2, 2015. 2. European Medicines Agency. www.ema.europa.eu. Accessed March 2, 2015.

A Biomarker Is Defined As:

Food and Drug Administration:• “A biomarker that is measured in an analytical test system with well-

established performance characteristics and for which there is an established scientific framework or body of evidence that elucidates the physiologic, toxicologic, pharmacologic, or clinical significance of the test results”1

1. FDA Guidance for Industry. www.fda.gov. Accessed March 2, 2015. 2. European Medicines Agency. www.ema.europa.eu. Accessed March 2, 2015.

The PD-L1 IHC 28-8 pharmDx helps to determine whether non-squamous NSCLC patients should be considered for treatment with OPDIVO®, which may prolong their life

‘complementary test’

Approval Order Statement

Approval for the pd-l1 ihc 22c3 pharmdx. This device is indicated for thefollowing: pd-l1 ihc 22c3 pharmdx is a qualitative immunohistochemicalassay using monoclonal mouse anti-pd-l1, clone 22c3 antibody intendedfor use in the detection of pd-l1protein in formalin fixed, paraffinembedded (ffpe) non-small cell lung cancer (nsclc) tissue using envisionflex visualization system on autostainer link 48. Pd-l1 protein expressionis determined by using tumor proportion score (tps), which is thepercentage of viable tumor cells showing partial or complete membranestaining. The specimen should be considered pd-l1 positive if tps >= 50%of the viable tumor cells exhibit membrane staining at any intensity. Pd-l1 ihc 22c3 pharmdx is indicated as an aid in identifying nsclc patients fortreatment with keytruda (pembrolizumab)

companion diagnostics

Appl Immunohistochem Mol Morphol. 2016 Jul;24(6):392-7Roach C, et al

Appl Immunohistochem Mol Morphol. 2016 Jul;24(6):392-7Roach C, et al

Appl Immunohistochem Mol Morphol. 2016 Jul;24(6):392-7Roach C, et al

Formalin-fixed, paraffin-embedded tissues have been validated for use The paraffin temperature should not exceed 60 °

Fixation in 10% neutral buffered formalin for 12–72 hours. Fixation times of 3 hours or less should not be used for PD-L1 assessment.

The use of PD-L1 IHC 22C3 pharmDx on decalcified tissues or other fixatives has not been validated and is not recommended

Tissue Processing

Store tissue sections in the dark at 2–8 °C (preferred) or at roomtemperature up to 25 °C to preserve antigenicity, and stain within 6 monthsof sectioning.

To assess reagents

To assess reagents

• To monitor differences in processing and embedding include positive and negative in-house control tissue of the same tumor indication in each staining run, in addition to the PD-L1 IHC 22C3 pharmDx Control Cell Line Slide.

The ideal positive control tissue provides a complete dynamic representation of weak to moderate cell membrane staining.

The ideal negative control tissue gives no staining on tumor cellsbut contains tumor-associated macrophages/immune cellswhich may express PD-L1 and offer an internal positive control