Reproducibility and concordance of 4 clinically developed programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) assays in triple-negative breast cancer (TNBC)

Abstract Background Atezolizumab (an anti–PD-L1 antibody) has shown clinical activity alone or in combination with nab-paclitaxel in patients (pts) with first-line metastatic TNBC who have PD-L1 expression on their tumour-infiltrating immune cells (IC). We analysed the performance of 4 PD-L1 IHC assays for PD-L1 IC expression in TNBC. Methods Thirty archival TNBC tissue specimens were selected from a set of 107 based on PD-L1 IC expression per VENTANA SP142 ( 5%: 8 cases), to represent the distribution of PD-L1 IC–positivity in the pivotal atezolizumab studies (Emens et al., SABCS 2018; JAMA Oncol 2019). Serial histologic sections were stained with VENTANA SP142 and SP263, and DAKO 22C3 and 28-8, per manufacturer protocols. Slides were blinded for both assay and sample information and scored by trained readers at 7 sites for PD-L1 IC expression (% per tumour area), as well as tumour cell expression (≥1% vs Results Adjusted means of PD-L1 IC staining ranged from 3.7% to 7.8% (Table); SP263 stained more IC than the other assays. Pairwise comparison of adjusted means showed small, non-significant differences (–1.2% to 0.6%) between SP142, 22C3 and 28-8, but a significant increase in PD-L1 staining for SP263 vs the other assays (3.0% to 4.2%). Intra-class correlations (ICC) for the assays showed moderate (0.460) to excellent (0.805) reader concordance (Table). Pre-specified allocation to a 1% binary IC cut-off revealed good-to-high inter-reader agreement (Kappa 0.589 to 0.789). Table . 359P Assay PD-L1 on IC, % (95% CI) * Reader ICC (95% CI) † SP263 7.8 (7.1–8.6) 0.616 (0.477–0.758) SP142 4.3 (3.5–5.0) 0.805 (0.710–0.887) 22C3 3. 7 (2.9–4.4) 0.605 (0.474–0.755) 28-8 4.9 (4.1–5.6) 0.460 (0.319–0.636) * Sample and reader adjusted means; † Between 7 readers Conclusions The results of this first multicentre PD-L1 assay comparison study in TNBC indicate good-to-high reproducibility and concordance of PD-L1 IC expression between the SP142, 22C3 and 28-8 assays, while higher PD-L1 IC expression levels were detected with SP263. Hence, SP142, 22C3 and 28-8 may be considered analytically interchangeable for PD-L1 IC testing. Clinical trial identification Roche study ID SL41336. Editorial acknowledgement Support for third-party writing assistance for this abstract, furnished by Katie Wilson, PhD, of Health Interactions, was provided by Roche Pharma AG, Grenzach-Wyhlen, Germany. Legal entity responsible for the study F. Hoffmann-La Roche Ltd. Funding Roche Pharma AG, Grenzach-Wyhlen, Germany. Disclosure A. Noske: Travel / Accommodation / Expenses: Roche; Non-remunerated activity/ies, Support for third-party medical writing assistance: Roche Pharma AG, Germany. J. Ammann: Full / Part-time employment: Roche Pharma AG, Germany; Shareholder / Stockholder / Stock options: Roche; Non-remunerated activity/ies, Support for third-party medical writing assistance: Roche Pharma AG, Germany. D. Wagner: Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Non-remunerated activity/ies, Support for third-party medical writing assistance: Roche Pharma AG, Germany. C. Denkert: Honoraria (institution): Teva; Honoraria (self): Roche; Honoraria (self): Celgene; Honoraria (self): Amgen; Advisory / Consultancy: Daiichi; Advisory / Consultancy: MSD; Shareholder / Stockholder / Stock options: Sividon Diagnostics; Shareholder / Stockholder / Stock options: Myriad; Non-remunerated activity/ies, Support for third-party medical writing assistance: Roche Pharma AG. A. Lebeau: Advisory / Consultancy: Roche Pharma AG, Germany; Advisory / Consultancy: Novartis; Research grant / Funding (self): Roche Pharma AG, Germany; Research grant / Funding (self): Sysmex Europe; Research grant / Funding (self): BioNTech Diagnostics; Travel / Accommodation / Expenses: Roche Pharma AG, Germany; Travel / Accommodation / Expenses: Novartis; Non-remunerated activity/ies, Support for third-party medical writing assistance: Roche Pharma AG, Germany. P. Sinn: Honoraria (self), Research grant / Funding (self), Travel / Accommodation / Expenses: Roche; Honoraria (institution), Travel / Accommodation / Expenses: Nanostring; Honoraria (self), Travel / Accommodation / Expenses: Genomic Health; Research grant / Funding (self): Dietmar-Hopp-Stiftung; Full / Part-time employment: Univ. Heidelberg; Non-remunerated activity/ies, Support for third-party medical writing assistance: Roche Pharma AG, Germany. H. Kreipe: Advisory / Consultancy: Roche Pharma AG, Germany; Advisory / Consultancy: Novartis; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Genomic Health; Non-remunerated activity/ies, Support for third-party medical writing assistance: Roche Pharma AG, Germany. G. Baretton: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): MSD; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Pfizer; Non-remunerated activity/ies, Support for third-party medical writing assistance: Roche Pharma AG, Germany. K. Steiger: Research grant / Funding (institution): Roche; Research grant / Funding (institution): BMS; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Bruker Daltonics; Non-remunerated activity/ies, Support for third-party medical writing assistance: Roche Pharma AG, Germany. M. Kiechle: Honoraria (self), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Travel / Accommodation / Expenses: Myriad; Research grant / Funding (self): German Cancer Aid; Research grant / Funding (self): DFG; Shareholder / Stockholder / Stock options: Therawis Diagnostics GmBH; Non-remunerated activity/ies, Support for third-party medical writing assistance: Roche Pharma AG, Germany. S. Hieke-Schulz: Full / Part-time employment: Roche Pharma AG, Germany; Non-remunerated activity/ies, Support for third-party medical writing assistance: Roche Pharma AG, Germany. W. Roth: Honoraria (self): Roche; Honoraria (self): AstraZeneca; Honoraria (self): MSD; Honoraria (self): Merck; Honoraria (self): Bayer; Honoraria (self): Novartis; Honoraria (self): Chugai; Non-remunerated activity/ies, Support for third-party medical writing assistance: Roche Pharma AG, Germany. W. Weichert: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Merck; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy: Celgene; Speaker Bureau / Expert testimony: Boehringer; Speaker Bureau / Expert testimony: Lilly; Speaker Bureau / Expert testimony: Takeda; Speaker Bureau / Expert testimony: Amgen; Research grant / Funding (institution): Bruker Daltonics; Non-remunerated activity/ies, Support for third-party medical writing assistance: Roche Pharma AG, Germany.