Integrating Companion Diagnostic Assays into Drug Development: Addressing the Challenges from the Diagnostic Perspective

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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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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