Development of a programmed cell death ligand-1 immunohistochemical assay validated for analysis of non-small cell lung cancer and head and neck squamous cell carcinoma

Rebelatto, Marlon C.; Midha, Anita; Mistry, Amita; Sabalos, Constantine; Schechter, Nicole; Li, Xia; Jin, Xiaoping; Steele, Keith; Robbins, Paul B.; Blake-Haskins, John A.; Walker, Jill

doi:10.1186/s13000-016-0545-8

Cited by 165 publications

(174 citation statements)

References 52 publications

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“…The H-score has been applied in many IHC studies for its semi-quantitative characteristic3940. Since no standard scoring criteria for PD-1 and PD-L1 are available353841, we have used an ROC analysis to determine the cut-off value for PD-1 and PD-L1.…”

Section: Discussionmentioning

confidence: 99%

PD-L1 predicts poor prognosis for nasopharyngeal carcinoma irrespective of PD-1 and EBV-DNA load

Zhou

Shi

Miao

et al. 2017

Sci Rep

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Programmed death-1 (PD-1) is an immunosuppressive receptor functionally bound with programmed death-ligand 1 (PD-L1), which has been reported in various malignancies. However, only a few studies are available for the clinical significance of PD-1/PD-L1 in nasopharyngeal carcinoma (NPC). In this study, we aim to investigate alterations in PD-1/PD-L1 by using immunohistochemistry analysis in a cohort of consecutively enrolled NPC patients (n = 99). To further analyse the correlation between PD-1/PD-L1 and factors involved in clinico-pathology, haematologic biomarkers, EBV-DNA load and outcomes, we collected clinical data for statistical analysis. We observed that lower haemoglobin (HB) and Body Mass Index (BMI) levels were associated with high levels of PD-L1 staining in NPC patients. Importantly, our results suggested that PD-L1 might be a negative indicator for NPC patients. In contrast, a correlation between the PD-1/PD-L1 level and EBV load was not identified. Moreover, PD-1 positivity was suggested to not be significantly correlated with clinical outcomes. Taken together, our results revealed that PD-L1 might be a potential prognostic biomarker for NPC patients. However, further studies are needed to clarify the underlying mechanism of EBV status in the immunosuppression process induced by the PD-1/PD-L1 axis.

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Section: Discussionmentioning

confidence: 99%

PD-L1 predicts poor prognosis for nasopharyngeal carcinoma irrespective of PD-1 and EBV-DNA load

Zhou

Shi

Miao

et al. 2017

Sci Rep

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“…Staining cutoffs are used to classify patients with high or low/no tumor PD-L1 expression (20,23), and the cutoff appropriate for clinical decision making for each PD-1 or PD-L1 therapy is determined by clinical data.…”

Section: Discussionmentioning

confidence: 99%

“…In NSCLC, knowledge of PD-L1 expression levels can inform treatment decisions and therefore assays are needed that reliably and accurately measure tumor PD-L1 expression levels (20). Several PD-L1 assays are in development with further FDA approvals in NSCLC anticipated within the next few years.…”

Section: Introductionmentioning

confidence: 99%

“…In addition to the Dako assays approved for use with pembrolizumab and nivolumab (10,13) and the VENTANA PD-L1 (SP142) Assay approved for use with atezolizumab (22), the VENTANA PD-L1 (SP263) Assay is in development for use with durvalumab (20). Each assay uses different antibody clones, IHC protocols, scoring algorithms, and cutoffs for PD-L1 positivity (refs.…”

Section: Introductionmentioning

confidence: 99%

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Agreement between Programmed Cell Death Ligand-1 Diagnostic Assays across Multiple Protein Expression Cutoffs in Non–Small Cell Lung Cancer

Ratcliffe

Sharpe

Midha

et al. 2017

Clinical Cancer Research

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Purpose: Immunotherapies targeting programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) demonstrate encouraging antitumor activity and manageable tolerability in non–small cell lung cancer (NSCLC), especially in patients with high tumor PD-L1 expression, as detected by companion or complementary diagnostic assays developed for individual agents. A laboratory is unlikely to use multiple assay platforms. Furthermore, commercially available diagnostic assays are not standardized, and different assay methods could lead to inappropriate treatment selection. This study establishes the extent of concordance between three validated, commercially available PD-L1 IHC diagnostic assays for NSCLC patients [Ventana SP263 (durvalumab), Dako 22C3 (pembrolizumab), and Dako 28-8 (nivolumab)]. Experimental Design: Five hundred formalin-fixed, paraffin-embedded archival NSCLC samples were obtained from commercial sources. Stained slides were read in batches on an assay-by-assay basis by a single pathologist trained in all methods, in a Clinical Laboratory Improvements Amendments program–certified laboratory. An additional pathologist performed an independent review of 200 stained samples for each assay. Results: PD-L1 expression was evaluable with all assays in 493 samples. The three assays showed similar patterns of tumor membrane staining, with high correlation between percent PD-L1 staining. An overall percentage agreement of >90% was achieved between assays at multiple expression cutoffs, including 1%, 10%, 25%, and 50% tumor membrane staining. Conclusions: This study builds optimism that harmonization between assays may be possible, and that the three assays studied could potentially be used interchangeably to identify patients most likely to respond to anti-PD-1/PD-L1 immunotherapies, provided the appropriate clinically defined algorithm and agent are always linked. Clin Cancer Res; 23(14); 3585–91. ©2017 AACR.

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“…Its companion IHC biomarker assay is Roche Ventana SP263 [47]. The SP263 PD-L1 positivity cutoff is 25% for NSCLC.…”

Section: Current Pd-1/pd-l1 Bioassaysmentioning

confidence: 99%

Utility of PD-L1 immunohistochemistry assays for predicting PD-1/PD-L1 inhibitor response

2017

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We have seen a notable increase in the application of PD-1/PD-L1 inhibitors for the treatment of several solid and hematogenous malignancies including metastatic melanoma, non-small-cell lung cancer and lymphoma to name a few. The need for biomarkers for identification of a suitable patient population for this type of therapy is now pressing. While specific biomarker assays have been developed for these checkpoint inhibitors based on their respective epitopes, the available studies suggested the clinical utility of these biomarker assays is for response stratification and not patient selection. Further improvement in assay development is needed to utilize this type of assay in identification of ideal patient population for this therapy.

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Development of a programmed cell death ligand-1 immunohistochemical assay validated for analysis of non-small cell lung cancer and head and neck squamous cell carcinoma

Cited by 165 publications

References 52 publications

PD-L1 predicts poor prognosis for nasopharyngeal carcinoma irrespective of PD-1 and EBV-DNA load

PD-L1 predicts poor prognosis for nasopharyngeal carcinoma irrespective of PD-1 and EBV-DNA load

Agreement between Programmed Cell Death Ligand-1 Diagnostic Assays across Multiple Protein Expression Cutoffs in Non–Small Cell Lung Cancer

Utility of PD-L1 immunohistochemistry assays for predicting PD-1/PD-L1 inhibitor response

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