Comparison of patient populations identified by different PD-L1 assays in in triple-negative breast cancer (TNBC)

M Scott P Scorer C Barker H Al-Masri

Annals of Oncology, Volume 30, Issue Supplement_3, May 2019, mdz095.009, https://doi.org/10.1093/annonc/mdz095.009

Published:

 

13 May 2019

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Topic:

 

• triple-negative breast cancer
• programmed cell death 1 ligand 1

Issue Section:

 Biomarkers, translational research and precision medicine

Background: TNBC represents an unmet clinical need; the IMPassion 130 and KEYNOTE-086 trials have demonstrated efficacy of PD-1/PD-L1 targeted therapeutics in the metastatic/unresectable first line setting, with increased response in PD-L1 high populations, defined using different diagnostic assays and algorithms. This work addresses the need to establish PD-L1 assay concordance in TNBC.

Methods: 196 TNBC cases were stained by IHC using the VENTANA PD-L1 (SP263), VENTANA PD-L1 (SP142), Dako PD-L1 IHC 28-8 pharmDx and Dako PD-L1 IHC 22C3 pharmDx assays. A single pathologist scored the proportions of membrane staining tumour cells (TC), staining immune cells (IC) and tumour occupied by immune cells. The proportion of tumour occupied by staining immune cells (IC_TA) and Combined Positive Score (CPS) were derived. Concordance between assays was evaluated using the Spearman coefficient ρ. Concordance in patient status was assessed using overall, positive and negative percent agreement (OPA/PPA/NPA) at matched algorithms and cut-offs.

Results: SP263, 22C3 and 28-8 assays showed good analytical correlation for TC staining (ρ = 0.84–0.89), but lower for SP142 (0.44-0.46), whereas all assays showed good correlation for IC_TA(0.77-0.96) and CPS (0.78-0.95). OPA ranged from 58%–97% at matched algorithms (Table). Prevalence for SP142 IC_TA≥1% and 22C3 CPS≥1 was in-line with IMPassion 130 and KEYNOTE-086, respectively.

Conclusions: Analytical performance between SP263, 22C3 and 28-8 is very similar; SP142 stains fewer TCs and ICs. In contrast to other cancer types, in TNBC, TC scores are lower and IC scores are higher. Care should be taken when interchanging PD-L1 assays and interpreting efficacy data derived with different algorithms in TNBC; whilst SP263 would identify largely the same PD-L1 patient population as on KEYNOTE-086, it could potentially identify 22% additional cases as PD-L1 high than on IMPassion 130.

Legal entity responsible for the study: AstraZeneca.

Funding: AstraZeneca.

Disclosure: M. Scott, P. Scorer, C. Barker: Employee, shareholder: AstraZeneca. H. Al-Masri: Employee: Hematogenix.

Table: 10O 

Prevalence (%) and OPA (%) of VENTANA SP263 with other assays at matched cut-offs

	SP263	22C3	22C3	28-8	28-8	SP142	SP142
Cut-off	Prevalence	Prevalence	OPA	Prevalence	OPA	Prevalence	OPA
TC ≥ 1%	53	50	91	46	88	11	58
ICTA≥1%	54	51	96	52	97	32	78
CPS≥1	64	60	92	61	95	35	71

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