A retrospective cohort study of PD-L1 prevalence, molecular associations and clinical outcomes in patients with NSCLC: Results from the European Thoracic Oncology Platform (ETOP) Lungscape Project

Kerr, Keith M.; Thunnissen, Erik; Dafni, Urania; Finn, Stephen; Bubendorf, Lukas; Soltermann, Alex; Verbeken, Eric; Biernat, Wojciech; Warth, Arne; Marchetti, Antonio; Speel, Ernst‐Jan M.; Pokharel, S.; Quinn, Anne Marie; Monkhorst, Kim; Navarro, Atilio; Madsen, Line Bille; Radonic, Teodora; Wilson, Joan; Luca, Graziano De; Gray, Steven G.; Cheney, Richard; Savic, Spasenija; Martorell, Miguel; Muley, Thomas; Baas, Paul; Meldgaard, Peter; Blackhall, Fiona; Dingemans, Anne‐Marie C.; Dziadziuszko, Rafał; Vansteenkiste, Johan; Weder, Walter; Polydoropoulou, Varvara; Geiger, Thomas; Kammler, Roswitha; Peters, Solange; Stahel, Rolf A.

doi:10.1016/j.lungcan.2019.03.012

Cited by 42 publications

(28 citation statements)

References 36 publications

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“…[ 29 – 35 ] On the contrary, three studies of Western and Australian patient cohorts found PD-L1 expression as a favorable prognostic factor [ 36 – 38 ]. In the largest Western cohort of surgically resected stage I–III NSCLC cases in European Thoracic Oncology Platform (ETOP) Lungscape Project, 2008 evaluable cases were assessed regarding PD-L1 expression [ 36 ]. PD-L1 positivity prevalence of 1% and 50% cut-off was 43.4% and 16.6%, respectively, but was significantly more frequent in higher stages.…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of PD-L1 expression in patients with unresectable stage III non-small cell lung cancer treated with chemoradiotherapy

2020

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Background Expression of PD-L1 is the most investigated predictor of benefit from immune checkpoint blockade in advanced NSCLC but little is known about the association of PD-L1 expression and clinicopathological parameters of patients with unresectable stage III NSCLC. Methods National registry data was searched for medical records of consecutive inoperable stage III NSCLC patients treated with ChT and RT from January 2012 to December 2017. Totally 249 patients were identified that met inclusion criteria and of those 117 patients had sufficient tissue for PD-L1 immunohistochemical staining. Results Eighty patients (68.4%) expressed PD-L1 of ≥ 1% and 29.9% of more than 50%. Median PFS was 15.9 months in PD-L1 negative patients and 16.1 months in patients with PD-L1 expression ≥ 1% (p = 0.696). Median OS in PD-L1 negative patients was 29.9 months compared to 28.5 months in patients with PD-L1 expression ≥ % (p = 0.888). There was no difference in median OS in patients with high PD-L1 expression (≥ 50%) with 29.8 months compared to 29.9 months in those with low (1–49%) or no PD-L1 expression (p = 0.694). We found that patients who received a total dose of 60 Gy or more had significantly better median OS (32 months vs. 17.5 months, p < 0.001) as well as patients with PS 0 (33.2 vs. 20.3 months, p = 0.005). Conclusions In our patients PD-L1 expression had no prognostic value regarding PFS and OS. Patients with good performance status and those who received a total radiation dose of more than 60 Gy had significantly better mOS.

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Section: Discussionmentioning

confidence: 99%

Prognostic value of PD-L1 expression in patients with unresectable stage III non-small cell lung cancer treated with chemoradiotherapy

2020

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“…If concordance is less than 90%, laboratories need to investigate the cause of low concordance. The a priori chance for 90% concordance will be high if 55% PD‐L1 negative samples and 35% PD‐L1 strongly positive samples are examined . The composition of the case set varies from resection specimens only, to a mixture of small samples (with or without cytology) and resection specimens.…”

Section: Discussionmentioning

confidence: 99%

External quality assessment demonstrates that PD‐L1 22C3 and SP263 assays are systematically different

Dodson¹,

Parry²,

Lissenberg‐Witte

et al. 2019

The Journal of Pathology CR

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PD-L1 inhibitors are part of first line treatment options for patients with advanced non-small cell lung cancer. PD-L1 immunohistochemistry (IHC) assays act as either a companion or a complementary diagnostic. The purpose of this study is to describe the experience of external quality assurance (EQA) provider UK NEQAS ICC and ISH with the comparison of different PD-L1 assays used in daily practice. Three EQA rounds (pilot, run A and run B) were carried out using formalin fixed paraffin embedded samples with sample sets covering a range of epitope concentrations, including 'critical samples' near to clinical threshold cut-offs. An expert panel (n = 4) evaluated all returned slides simultaneously and independently on a multi-header microscope together with the participants own in-house control material. The tonsil sample was evaluated as 'acceptable' or 'unacceptable', and for the other samples the percentage of PD-L1 stained tumour cells were estimated in predetermined categories (<1%, 1 to <5%, 5 to <10%, 10 to <25%, 25 to <50%, 50 to <80%, 80 to 100%). In the pilot and the two subsequent runs the number of participating laboratories was 43, 69 and 76, respectively. The pass rate for the pilot run was 67%; this increased to 81% at run A and 82% at run B. For two 'critical samples', in runs A and B, 22C3 IHC had significantly higher PD-L1 expression than SP263 IHC (p < 0.001), whilst the PD-L1 scores for the other six samples were similar for all assays. In run A the laboratory developed tests (LDTs) using 22C3 scored lower than the commercial 22C3 tests (p = 0.01). After the initial testing, improvement in performance of PD-L1 IHC is shown for approved and LDT PD-L1 assays. Equivalency of approved PD-L1 22C3 and SP263 assays cannot be assumed as the scores cross the clinically relevant thresholds of 1% and 50% PD-L1 expression.

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“…Concerning the correlation between PTEN and PD-L1 in lung cancer, conflicting results have been proposed [87,88]. Interestingly, Hlaing and coworkers observed a positive correlation between PTEN expression and PD-L1 level, differently from the previously reported data for other tumor types, with a 80% of correlation observed in the squamous histology [88].…”

Section: Pten Loss Can Modify the Tumor Microenvironmentmentioning

confidence: 99%

PTEN Alterations as a Potential Mechanism for Tumor Cell Escape from PD-1/PD-L1 Inhibition

Cretella

Digiacomo

Giovannetti

et al. 2019

Cancers

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The recent approval of immune checkpoint inhibitors drastically changed the standard treatments in many advanced cancer patients, but molecular changes within the tumor can prevent the activity of immunotherapy drugs. Thus, the introduction of the inhibitors of the immune checkpoint programmed death-1/programmed death ligand-1 (PD-1/PD-L1), should prompt deeper studies on resistance mechanisms, which can be caused by oncogenic mutations detected in cancer cells. PTEN, a tumor suppressor gene, dephosphorylates the lipid signaling intermediate PIP3 with inhibition of AKT activity, one of the main effectors of the PI3K signaling axis. As a consequence of genetic or epigenetic aberrations, PTEN expression is often altered, with increased activation of PI3K axis. Interestingly, some data confirmed that loss of PTEN expression modified the pattern of cytokine secretion creating an immune-suppressive microenvironment with increase of immune cell populations that can promote tumor progression. Moreover, PTEN loss may be ascribed to reduction of tumor infiltrating lymphocytes (TILs), which can explain the absence of activity of immune checkpoint inhibitors. This review describes the role of PTEN loss as a mechanism responsible for resistance to anti PD-1/PD-L1 treatment. Moreover, combinatorial strategies between PD-1/PD-L1 inhibitors and PI3K/AKT targeting drugs are proposed as a new strategy to overcome resistance to immune checkpoint inhibition.

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A retrospective cohort study of PD-L1 prevalence, molecular associations and clinical outcomes in patients with NSCLC: Results from the European Thoracic Oncology Platform (ETOP) Lungscape Project

Cited by 42 publications

References 36 publications

Prognostic value of PD-L1 expression in patients with unresectable stage III non-small cell lung cancer treated with chemoradiotherapy

Prognostic value of PD-L1 expression in patients with unresectable stage III non-small cell lung cancer treated with chemoradiotherapy

External quality assessment demonstrates that PD‐L1 22C3 and SP263 assays are systematically different

PTEN Alterations as a Potential Mechanism for Tumor Cell Escape from PD-1/PD-L1 Inhibition

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