Abstract B005: An immunohistochemical PD-L1 companion diagnostic assay for treatment with durvalumab (MEDI4736) in NSCLC patients

46 Background: Following the recent approval of several companion diagnostic and complementary diagnostic assays for PD-L1 expression testing, as well as the availability of multiple antibodies for use in laboratory testing, pathologists have a range of tools at their disposal for measuring expression levels of this predictive biomarker. While specific cut-off points for positivity are specified by the assay manufacturer and/or recommended based on trial data, clinicians can choose different cut-off points to define positivity. In this study, we explore the variety of test brands and cut-off points that are being used in clinical practice in the US by examining real-world usage data. Methods: Between June and August 2016, a panel of pathologists (n = 27) in the US were asked to report on their practices relating to PD-L1 expression testing for NSCLC patients, through the submission of online de-identified record forms (n = 167 PD-L1-tested samples). Results: Of the 167 samples, 112 (67%) were tested with the Dako 22C3 pharmDx assay, 37 (22%) with the Dako 28-8 pharmDx assay and 16 (10%) with a lab-developed test (LDT). When using 22C3 pharmDx, 72% of samples were tested with the recommended 50% cut-off point, with the remaining 28% using lower cut-off points, ranging from 1% to 25%. For 28-8 pharmDx, both the 1% cut-off point (in 54% of cases) and the 5% cut-off point (in 35% of cases) were frequently used (1% recommended; 5% being investigated in clinical trials e.g. CHEKMATE-026). LDTs were mostly (88%) employed with a cut-off of 1% across antibodies. Conclusions: The use of PD-L1 expression testing to determine eligibility for PD-(L)1 inhibitors in the clinical setting shows significant fragmentation in the US, with multiple different assays being employed. Furthermore, there is a lack of standardization in terms of the cut-off points that are used when testing with each of those assays. This lack of consistency adds a level of complexity to oncologists treatment decisions when choosing whether or not to treat with a PD-(L)1 inhibitor, and which brand to choose.

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The “eyes” have it?—intra- and inter-observer reproducibility of the PD-L1 companion diagnostic assay

Translational Cancer Research ◽

10.21037/tcr.2017.07.06 ◽

2017 ◽

Vol 6 (S6) ◽

pp. S1027-S1029

Author(s):

Steven G. Gray ◽

Mark C. Wright ◽

Stephen P. Finn

Keyword(s):

Diagnostic Assay ◽

Companion Diagnostic

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Association of gene expression module biomarkers with clinical and therapeutic endpoints and their use with a universal companion diagnostic assay.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.27_suppl.228 ◽

2011 ◽

Vol 29 (27_suppl) ◽

pp. 228-228

Author(s):

S. A. Tomlins ◽

P. Williams ◽

S. Sadis ◽

P. Wyngaard ◽

K. Oades ◽

...

Keyword(s):

Gene Expression ◽

Meta Analysis ◽

Expression Patterns ◽

Response To Therapy ◽

Clinical Samples ◽

Molecular Heterogeneity ◽

Diagnostic Assay ◽

Companion Diagnostics ◽

Genomic Signatures ◽

Companion Diagnostic

228 Background: Gene expression patterns are increasingly capable of stratifying patients based on prognosis and response to therapy. Given the limited availability of sample tissue, however, it is not feasible to utilize every test for every patient, suggesting the need for a universal companion diagnostic assay that is informative with respect to multiple clinical and therapeutic endpoints. Key challenges are identification of appropriate gene expression biomarkers, translation of biomarkers to clinical assays, and development of reliable gene expression profiling of formalin-fixed clinical specimens. Here we describe a novel RT-PCR biomarker assay optimized for FFPE clinical samples that has broad prognostic and predictive potential. Methods: A co-expression meta-analysis of 5,339 breast tumors from 56 microarray datasets identified highly co-expressed sets of genes (modules) across multiple datasets. Module biomarkers were tested for their ability to associate with prognostic and predictive targets in published datasets. In addition, each module was reduced from 10–1000 genes to 2-3 genes for use in companion diagnostic assays based on degree of co-expression across the meta-analysis, and validated against an independent panel of tumor samples. Results: This study demonstrates that a single test utilizing multiple module biomarkers is informative with respect to standard parameters such as ER, PR and Her2, and in addition reproduces existing prognostic and predictive genomic signatures. Furthermore, we show that modules of 10-1000 genes can be represented by 2-3 genes for direct use in companion diagnostics development. Conclusions: The molecular heterogeneity of breast cancer can be summarized by discrete gene expression modules that individually represent distinct biological programs, and that collectively can be represented by as few as 96 genes. Modules, together with outlier genes, allow for summation of the entire transcriptional program and provide a universal assay with broad application to companion diagnostics development.

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Anti-PD-1/PD-L1 Therapy for Non-Small-Cell Lung Cancer: Toward Personalized Medicine and Combination Strategies

Journal of Immunology Research ◽

10.1155/2018/6984948 ◽

2018 ◽

Vol 2018 ◽

pp. 1-17 ◽

Cited By ~ 48

Author(s):

Hongshu Sui ◽

Ningxia Ma ◽

Ying Wang ◽

Hui Li ◽

Xiaoming Liu ◽

...

Keyword(s):

Lung Cancer ◽

Targeted Therapy ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Small Cell Lung ◽

Diagnostic Assays ◽

Programmed Death ◽

Companion Diagnostic ◽

Nsclc Patients

Lung cancer remains a leading cause of cancer-related mortality worldwide with the poor prognosis. Encouragingly, immune checkpoint blockade targeting programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) has dramatically changed the landscape for treatments in patients with non-small-cell lung cancer (NSCLC). However, only a small proportion of NSCLC patients responded to monotherapy of anti-PD-1/PDL1 agents; together, the development of resistance to anti-PD-1/PD-L1 therapy that leads to failure of anti-PD-1/PD-L1 therapy has significantly limited a broad applicability of the findings in clinical practices. Nowadays, several companion diagnostic assays for PDL1 expression have been introduced for identifying patients who may benefit the immunotherapy. In addition, results from clinical trials explored combinatory therapeutic strategies with conventional and/or targeted therapy reported a higher efficacy with an acceptable safety profile in NSCLC treatments, as compared to the monotherapy of these agents alone. In this review article, we summarized several anti-PD-1/PD-L1 agents licensed for NSCLC treatment, with a focus on predictive biomarkers and companion diagnostic assays for identification of NSCLC patients for immunotherapy anti-PD-1/PDL1 antibodies. Of a great interest, potentials of the combinatory therapy of anti-PD-1/PDL1 therapy with a conventional or targeted therapy, or other immunotherapy such as CAR-T cell therapy were emphasized in the article.

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