SP142 PD-L1 Scoring Shows High Interobserver and Intraobserver Agreement in Triple-negative Breast Carcinoma But Overall Low Percentage Agreement With Other PD-L1 Clones SP263 and 22C3.

SP142 programmed cell death ligand 1 (PD-L1) status predicts response to atezolizumab in triple-negative breast carcinoma (TNBC). Prevalence of VENTANA PD-L1 (SP142) Assay positivity, concordance with the VENTANA PD-L1 (SP263) Assay and Dako PD-L1 IHC 22C3 pharmDx assay, and association with clinicopathologic features were assessed in 447 TNBCs. SP142 PD-L1 intraobserver and interobserver agreement was investigated in a subset of 60 TNBCs, with scores enriched around the 1% cutoff. The effect of a 1-hour training video on pretraining and posttraining scores was ascertained. At a 1% cutoff, 34.2% of tumors were SP142 PD-L1 positive. SP142 PD-L1 positivity was significantly associated with tumor-infiltrating lymphocytes (P <0.01), and node negativity (P=0.02), but not with tumor grade (P=0.35), tumor size (P=0.58), or BRCA mutation (P=0.53). Overall percentage agreement (OPA) for intraobserver and interobserver agreement was 95.0% and 93.7%, respectively, among 5 pathologists trained in TNBC SP142 PD-L1 scoring. In 5 TNBC SP142 PD-L1-naive pathologists, significantly higher OPA to the reference score was achieved after video training (posttraining OPA 85.7%, pretraining OPA 81.5%, P<0.05). PD-L1 status at a 1% cutoff was assessed by SP142 and SP263 in 420 cases, and by SP142 and 22C3 in 423 cases, with OPA of 88.1% and 85.8%, respectively. The VENTANA PD-L1 (SP142) Assay is reproducible for classifying TNBC PD-L1 status by trained observers; however, it is not analytically equivalent to the VENTANA PD-L1 (SP263) Assay and Dako PD-L1 IHC 22C3 pharmDx assay.

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Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.

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Conflicts of Interest and Source of Funding: Supported by Roche Products Pty. Limited (Australia) who is the study sponsor. kConFab is supported by a grant from the National Breast Cancer Foundation, and previously by the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania, and South Australia, and the Cancer Foundation of Western Australia. S.B.F. is funded by the NHMRC Practitioner Fellowship (APP 1079329). S.A.O.T. is funded by the National Breast Cancer Foundation (PRAC 16-006 and IIRS-19-84) and the Sydney Breast Cancer Foundation. S.A.O.T. has received travel/accommodation support from Roche for study participation and has received honorarium for participation in Advisory Boards from Roche, BMS and Merck. B.C. is a full-time employee of Roche. P.B. is an employee of OzBiostats Pty. Limited, who were contracted by Roche to work on the study. J.A., W.A.C., E.K.A.M., W.R., and V.S. have received travel/accommodation support from Roche for study participation. S.R.L. has received honorarium for participation in the Roche Advisory Board (2020) on HER2 and TNBC; is a member of the board of directors Breast Cancer Trials (formerly ANZ Breast Cancer Trial Group); and has received travel/accommodation support from Roche for study participation. J.B. has received honorarium and travel/accommodation support from Roche. For the remaining authors none were declared.