Companion and Complementary Diagnostics–Focus on PD-L1 Expression Assays for PD-1/PD-L1 Checkpoint Inhibitors in Non–Small Cell Lung Cancer

Hersom, Maria; Jørgensen, Jan Trøst

doi:10.1097/ftd.0000000000000460

Cited by 83 publications

(57 citation statements)

References 29 publications

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“…However, it is not easy to use CRP or NLR for appropriate drug selection because SIR markers are non‐specific. Accordingly, companion diagnostics might become more common in the urological cancer field; for example, detection of PD‐L1 protein in formalin‐fixed, paraffin‐embedded non‐small cell lung cancer tissue is essential for treatment with pembrolizumab in patients with non‐small cell lung cancer . As suggested by Rossi et al .…”

Section: Resultsmentioning

confidence: 99%

“…Accordingly, companion diagnostics might become more common in the urological cancer field; for example, detection of PD-L1 protein in formalin-fixed, paraffin-embedded non-small cell lung cancer tissue is essential for treatment with pembrolizumab in patients with non-small cell lung cancer. 167 As suggested by Rossi et al and Seah et al, follow up using SIR markers after treatment might be one of the ways that SIR markers can be used in clinical practice for therapeutic monitoring and decision-making regarding appropriate timing for changes in medication. 127,128 Further studies assessing changes of SIR markers over time would be expected.…”

Section: Resultsmentioning

confidence: 99%

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Role of systemic inflammatory response markers in urological malignancy

Ohno

2018

Int J of Urology

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The systemic inflammatory response is associated with survival in patients with a variety of cancers. This inflammatory response is measured in the peripheral blood, and can be monitored using two categories of indices: concentration of specific serum proteins (albumin, C‐reactive protein) and differential blood cell count (neutrophils, lymphocytes and platelets). Furthermore, combinations of these indices, such as the Glasgow Prognostic Score, which consists of the serum C‐reactive protein and albumin level; the neutrophil‐to‐lymphocyte ratio; the platelet‐to‐lymphocyte ratio; and the prognostic nutritional index, which is based on peripheral blood lymphocyte count and serum albumin level, have also been evaluated and compared in cancer research. To date, there are hundreds of studies that have shown the prognostic value of systemic inflammatory response markers in patients with urological cancer. Most studies have evaluated the prognostic and predictive role of the pretreatment value of the markers, although some have focused on the role of the post‐treatment value at specific points during the clinical course. The advantages of systemic inflammatory response markers are that they are easily measurable and inexpensive in the clinical setting. However, it is important to consider how clinicians use these markers in clinical practice. The present review provides a concise overview regarding systemic inflammatory markers in urological cancers, specifically C‐reactive protein, Glasgow Prognostic Score/modified Glasgow Prognostic Score, neutrophil‐to‐lymphocyte ratio, platelet‐to‐lymphocyte ratio and prognostic nutritional index.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Role of systemic inflammatory response markers in urological malignancy

Ohno

2018

Int J of Urology

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“…While the 22C3 assay is approved by the US FDA as a companion diagnostic to identify non-small cell lung carcinoma patients and gastroesophageal carcinoma patients prone to respond to pembrolizumab, 25 the SP142 assay is currently employed as a complementary diagnostic to define the likelihood of urothelial carcinoma patients to obtain clinical benefits from atezolizumab. 19 Previous clinical data indicate that an improved ORR to atezolizumab amongst urothelial carcinoma patients is associated with >5% positive staining for PD-L1 (as assessed by the SP142 assay) on tumor-infiltrating immune cells.…”

Section: Discussionmentioning

confidence: 99%

PD-L2 amplification and durable disease stabilization in patient with urothelial carcinoma receiving pembrolizumab

George

Papanicolau‐Sengos²,

Lenzo³

et al. 2018

OncoImmunology

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We report the immunological profile of a patient with upper-tract urothelial carcinoma experiencing stable disease on pembrolizumab for 20 months. The tumor exhibited extensive infiltration by CD8+ cytotoxic T lymphocytes, low-to-moderate mutational burden, no PD-L1 staining by commercially available immunohistochemical assays, but amplification of CD274 (coding for PD-L1) and/or PDCD1LG2 (encoding PD-L2) by fluorescence in situ hybridization. RNA-seq revealed multiple biomarkers of an ongoing immune response and compensatory immune evasion, including moderate PD-L1 levels coupled with robust PD-L2 expression. Pending validation in additional patients, these findings suggest that PD-L2 expression levels may constitute a biomarker of response to immune checkpoint blockade in urothelial carcinoma.

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“…The percentage of PD‐L1‐positivity in cancer cells, named the tumor proportion score (TPS), is also considered a predictive biomarker for anti‐PD‐1/PD‐L1 therapy in lung cancer . Several monoclonal antibodies such as 22C3, 28‐8, SP263, and SP142 have been used for immunohistochemistry (IHC) to detect PD‐L1 expression, and clones 22C3 and SP142 are now available for companion and complementary diagnostics . Several retrospective studies using pathological specimens have been published recently.…”

Section: Introductionmentioning

confidence: 99%

Accurate expression of PD‐L1/L2 in lung adenocarcinoma cells: A retrospective study by double immunohistochemistry

et al. 2019

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The percentage of programmed death ligand 1 (PD‐L1) positivity in cancer cells, named as the tumor proportion score, is considered to be a predictive biomarker for anti‐PD‐1/PD‐L1 therapy in lung cancer. PD‐L1 is expressed on not only cancer cells but also on immune cells, including macrophages. Although previous studies related to PD‐L1/2 expression in cancer tissues have been generally based on single immunohistochemistry (IHC), in the present study, we attempted to evaluate accurate PD‐L1/2 expression in cancer cells in lung adenocarcinoma cells using double IHC to also evaluate macrophages. Of the 231 patients, PD‐L1 expression was negative in 169 patients (73.2%), 1%‐49% positive in 47 patients (20.3%), and ≥50% positive in 15 patients (6.5%). Interestingly, PD‐L1 positivity was decreased when using double IHC compared with the estimation by single IHC. High PD‐L1 expression was associated with high‐grade cancer cells and in higher stage cancer. PD‐L2 was negative in 109 patients (47.2%), 1%‐49% positive in 50 patients (21.6%), and ≥50% positive in 72 patients (31.2%). The number of PD‐L2‐positive patients was increased in cases that had an epidermal growth factor receptor (EGFR) mutation and in lower stage cancer. Thirty‐five patients (15.2%) were positive for both PD‐L1 and PD‐L2, whereas 81 patients (35.1%) were negative for both PD‐L1 and PD‐L2. Log‐rank analysis showed that progression‐free survival and overall survival were significantly the longest in the PD‐L1‐negative and PD‐L2‐positive groups (P < .0001 and P = .0120). We observed lower PD‐L1 or PD‐L2 expression in lung adenocarcinoma than previously reported. Double IHC for macrophages may help clinicians to evaluate PD‐L1 or PD‐L2 expression specifically in cancer cells.

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Companion and Complementary Diagnostics–Focus on PD-L1 Expression Assays for PD-1/PD-L1 Checkpoint Inhibitors in Non–Small Cell Lung Cancer

Cited by 83 publications

References 29 publications

Role of systemic inflammatory response markers in urological malignancy

Role of systemic inflammatory response markers in urological malignancy

PD-L2 amplification and durable disease stabilization in patient with urothelial carcinoma receiving pembrolizumab

Accurate expression of PD‐L1/L2 in lung adenocarcinoma cells: A retrospective study by double immunohistochemistry

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