Download Non-Small Cell Lung Cancer (NSCLC)

Non-Small Cell
Lung Cancer (NSCLC)
PD-L1 BY IMMUNOHISTOCHEMISTRY
PD-1 and PD-L1
Programmed death 1 (PD-1) is an immune inhibitory receptor expressed on the surface of activated T-cells and mediates
suppression of the immune system.1 PD-1 interacts with the immunosuppressive PD-L1 ligand which is expressed on tumor
cells, inflammatory cells, and histiocytes, and inhibits T-cell activation.2
A new class of immunotherapies, PD-1 and PD-L1 inhibitors, blocks the interaction between PD-1 and PD-L1 on the tumor
cells and can enhance T-cell responses and mediate anti-tumor activity.1,2
The PD-1/PD-L1 Blockade
The PD-1/PD-L1 interaction protects
the cancer cell from immune destruction
Blocking the PD-1/PD-L1 interaction allows
T cells to destroy tumor cells
PD-L1 Expression

Tumor PD-L1 expression levels have been shown to be a predictive marker with response to several anti-PD1 antibodies1,2

PD-L1 expression can be measured by immunohistochemistry and detects PD-L1 expression in formalin-fixed, paraffinembedded NSCLC tumor tissue samples
Clinical Studies in NSCLC
Membranous PD-L1 expression (clone 22C3) and response to anti-PD1 immunotherapy KEYTRUDA® (pembrolizumab)
was evaluated in previously treated and untreated patients with metastatic NSCLC. The study results were as follows:2

37.6% of patients expressed PD-L1 in 1%–49% of neoplastic cells
(proportion score)

23.2% of patients expressed PD-L1 in ≥50% of neoplastic cells
(proportion score)

A PD-L1 proportion score of at least 50% was associated
with a higher response rate, longer progression-free survival,
and overall survival than those with scores below 50%

PD-L1 expression is independent of EGFR mutational status

PD-L1 expression was observed in a higher percentage
of patients with KRAS mutations
The DAKO PD-L1 IHC 22C3
pharmDxTM was recently FDA
approved as a companion
diagnostic assay to aid in
identifying advanced NSCLC
patients for treatment with
KEYTRUDA® (pembrolizumab).
continued on other side
Clinical Studies in NSCLC (cont’d)
Another study of patients with advanced non-squamous NSCLC,
PD-L1 expression (Clone 28-8), and response to anti-PD1 immunotherapy
nivolumab vs. chemotherapy, included the following results:3

46% of patients were negative for PD-L1 expression (<1%; OS HR 0.9)

54% of patients had ≥1% expression level (OS HR 0.59)

40% of patients had ≥5% expression level (OS HR 0.43)

36% of patients had ≥10% expression level (OS HR 0.4)

PD-L1 expression was associated with improved efficacy across
all endpoints (OS, PFS, duration of response) at all expression levels.
The most improvement was seen in patients with PD-L1 expression
≥5% and ≥10%, but was evident at PD-L1 expression levels as low as ≥1%.

Patients with tumors that had PD-L1 expression levels ≥1% were associated
with a doubling of overall median survival.
The DAKO PD-L1 IHC 28-8
pharmDxTM was recently
FDA-approved as a
complementary diagnostic
test to detect PD-L1 protein
expression levels, and
although not required for
nivolumab, the test is a new
tool that helps physicians
determine which patients
may benefit most from
treatment with nivolumab.
Specimen Requirement Options

Global Only

Tissue should be fixed in 10% neutral buffered formalin; alternative
fixatives have not been validated and may give erroneous results

A minimum of 100 cells is required
1) Fixed Paraffin Block with Corresponding H&E
2)Unstained Slides:
l
Minimum of 4 slides (include additional slide for H&E)
l
Pre-cut slides from paraffin block in 4-5 micron sections
and mount on plus (+) slides
REFERENCES
1.Kim, JW and Eder, JP, Prospects for Targeting PD-1 and PD-L1 in Various Tumor Types. Available on the website
of the Cancer Network. (http://www.cancernetwork.com/oncology-journal/prospects-targeting-pd-1-and-pd-l1various-tumor-types). Accessed July 8, 2015.
2. Garon, EB et al., Pembrolizumab for the Treatment of Non-Small-Cell Lung Cancer. N Engl J Med 2015; 372:2018-28.
3.Paz-Ares, L et al., Phase III, randomized trial (CheckMate 057) of nivolumab (NIVO) versus docetaxel (DOC) in
advanced non-squamous cell (non-SQ) non-small cell lung cancer (NSCLC). J Clin Oncol 33, 2015 (suppl; abstr LBA109).
KEYTRUDA® is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
pharmDx ® is a registered trademark of Dako A/S.
©2015 Laboratory Corporation of America ® Holdings. All rights reserved.
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