Prospective multi-institutional evaluation of pathologist assessment of PD-L1 assays for patient selection in triple negative breast cancer

Reisenbichler, Emily; Han, Gang; Bellizzi, Andrew M.; Bossuyt, Veerle; Brock, Jane E.; Cole, Kimberly; Fadare, Oluwole; Hameed, Omar; Hanley, Krisztina; Harrison, Beth T.; Kuba, María G.; Ly, Amy; Miller, Dylan V.; Podoll, Mirna; Roden, Anja C.; Singh, Kamaljeet; Sanders, Mary Ann; Wei, Shi; Wen, Hannah Y.; Pelekanou, Vasiliki; Yaghoobi, Vesal; Ahmed, Fahad Shabbir; Pusztai, Lajos; Rimm, David L.

doi:10.1038/s41379-020-0544-x

Cited by 112 publications

(129 citation statements)

References 13 publications

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“…Studies comparing PD-L1 assays performance on archival, routine clinical practice, and clinical trial TNBC samples have shown discrepancies among SP142, SP263, and 22C3 assays. PD-L1 positivity defined as the proportion of tumor area occupied by PD-L1-positive immune cells (IC A ) ≥1% with SP142 showed between 20 and 38, 10 and 35, and 7 and 19% fewer PD-L1+ cases compared to SP263 IC A ≥1% and 22C3 combined positive score (CPS) ≥1 and IC A ≥1%, respectively [22][23][24][25][26]. Prevalence with each assay is shown in Table 2.…”

Section: Technical Validation Phase: Analytical Validity Of Pd-l1 Ihcmentioning

confidence: 99%

“…Using SP142, the majority of non-neoplastic cells were CD68+, whereas 5% were CD8+ [48]. Two multi-institutional studies, [30] 24 TNBC IC A ≥1%: 50% TC ≥1%:17% (of which 92% were IC A ≥1%) NCT01375842 [7] 112 TNBC IC A ≥1%: 78%* KEYNOTE-119 NCT02555657 [31] 622 TNBC CPS ≥1: 65% CPS ≥10: 31% CPS ≥20: 18% KEYNOTE-012 NCT01848834 [32] 111 TNBC CPS ≥1: 59% KEYNOTE-086 NCT02447003 [33] 170 primary and metastatic samples TNBC [23,25]. Pathologists were trained on the evaluation of PD-L1 IHC and were required to pass a proficiency test in one of these studies [23].…”

Section: Technical Validation Phase: Analytical Validity Of Pd-l1 Ihcmentioning

confidence: 99%

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The path to a better biomarker: application of a risk management framework for the implementation of PD‐L1 and TILs as immuno‐oncology biomarkers in breast cancer clinical trials and daily practice

Gonzalez-Ericsson

Stovgaard

Sua

et al. 2020

The Journal of Pathology

168

132

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Immune checkpoint inhibitor therapies targeting PD-1/PD-L1 are now the standard of care in oncology across several hematologic and solid tumor types, including triple negative breast cancer (TNBC). Patients with metastatic or locally advanced TNBC with PD-L1 expression on immune cells occupying ≥1% of tumor area demonstrated survival benefit with the addition of atezolizumab to nab-paclitaxel. However, concerns regarding variability between immunohistochemical PD-L1 assay performance and inter-reader reproducibility have been raised. High tumor-infiltrating lymphocytes (TILs) have also been associated with response to PD-1/PD-L1 inhibitors in patients with breast cancer (BC). TILs can be easily assessed on hematoxylin and eosin-stained slides and have shown reliable inter-reader reproducibility. As an established prognostic factor in early stage TNBC, TILs are soon anticipated to be reported in daily practice in many pathology laboratories worldwide. Because TILs and PD-L1 are parts of an immunological spectrum in BC, we propose the systematic implementation of combined PD-L1 and TIL analyses as a more comprehensive immuno-oncological biomarker for patient selection for PD-1/PD-L1 inhibition-based therapy in patients with BC. Although practical and regulatory considerations differ by jurisdiction, the pathology community has the responsibility to patients to implement assays that lead to optimal patient selection. We propose herewith a riskmanagement framework that may help mitigate the risks of suboptimal patient selection for immuno-therapeutic approaches in clinical trials and daily practice based on combined TILs/PD-L1 assessment in BC.

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Section: Technical Validation Phase: Analytical Validity Of Pd-l1 Ihcmentioning

confidence: 99%

Section: Technical Validation Phase: Analytical Validity Of Pd-l1 Ihcmentioning

confidence: 99%

The path to a better biomarker: application of a risk management framework for the implementation of PD‐L1 and TILs as immuno‐oncology biomarkers in breast cancer clinical trials and daily practice

Gonzalez-Ericsson

Stovgaard

Sua

et al. 2020

The Journal of Pathology

168

132

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show abstract

“…Another example is represented by triple-negative breast cancers (TNBC), where the CDx test for this indication was PD-L1 (SP142) IHC Assay by using the immune cell (IC) scoring system [39]. IC scoring was considered as positive, for those with the presence of PD-L1 POS ICs that covered more than 1% of the tumour area (tumour cells, associated intratumoural and contiguous peritumoural stroma) [2]. The PD-L1 scoring systems are shown in Figure 2.…”

Section: Programmed Death Ligand 1 (Pd-l1)mentioning

confidence: 99%

“…Immune checkpoint inhibition has been increasingly applied in several solid tumours, with significant survival benefits, providing a precise patient selection [1][2][3]. Hence, not all the patients, even in the presence of similar clinical characteristics, would respond in the same way to the same immunotherapy protocol [4].…”

Section: Introductionmentioning

confidence: 99%

Biomarkers for precision immunotherapy in the metastatic setting: hope or reality?

Sajjadi¹,

Venetis²,

Scatena³

et al. 2020

ecancer

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Precision immunotherapy is a crucial approach to improve the efficacy of anti-cancer treatments, particularly in the metastatic setting. In this respect, accurate patient selection takes advantage of the multidimensional integration of patients' clinical information and tumourspecific biomarkers status. Among these biomarkers, programmed death-ligand 1, tumourinfiltrating lymphocytes, microsatellite instability, mismatch repair and tumour mutational burden have been widely investigated. However, novel tumour-specific biomarkers and testing methods will further improve patients' outcomes. Here, we discuss the currently available strategies for the implementation of a precision immunotherapy approach in the clinical management of metastatic solid tumours and highlight future perspectives.

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“…This challenge is especially problematic for biomarkers like PD‐L1 that are assessed at the protein level by immunohistochemistry. Currently, evaluation of these markers is semiquantitative at best, prone to subjectivity, 4‐6 and constrained by the number of markers that can be simultaneously or sequentially analyzed on each cell.…”

mentioning

confidence: 99%

Next‐generation FNA: Expanding the role of cytology in cancer immunotherapy

Nishino

Krane

2020

Cancer Cytopathology

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Prospective multi-institutional evaluation of pathologist assessment of PD-L1 assays for patient selection in triple negative breast cancer

Cited by 112 publications

References 13 publications

The path to a better biomarker: application of a risk management framework for the implementation of PD‐L1 and TILs as immuno‐oncology biomarkers in breast cancer clinical trials and daily practice

The path to a better biomarker: application of a risk management framework for the implementation of PD‐L1 and TILs as immuno‐oncology biomarkers in breast cancer clinical trials and daily practice

Biomarkers for precision immunotherapy in the metastatic setting: hope or reality?

Next‐generation FNA: Expanding the role of cytology in cancer immunotherapy

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