TY - JOUR
T1 - Equivalence of laboratory-developed test and PD-L1 IHC 22C3 pharmDx across all combined positive score indications
AU - Vainer, Gilad
AU - Huang, Lingkang
AU - Emancipator, Kenneth
AU - Nuti, Shanthy
N1 - Publisher Copyright:
© 2023 Vainer et al.
PY - 2023/6
Y1 - 2023/6
N2 - We conducted an analysis across multiple PD-L1 combined positive score (CPS) indications to establish concordance of a 22C3 antibody-based laboratory-developed test (LDT) on the Ventana BenchMark XT or BenchMark ULTRA platform and the regulatory-approved PD-L1 IHC 22C3 pharmDx in cervical cancer (CC), esophageal squamous cell carcinoma (ESCC), head and neck squamous cell carcinoma (HNSCC), triple-negative breast cancer (TNBC), and urothelial carcinoma (UC). Tumor specimens from each tumor type were stained with 22C3 antibody and scored using the 22C3 antibody-based LDT, and scores were compared with those using PD-L1 IHC 22C3 pharmDx. PD-L1 status was measured by the pathologist using CPS as a continuous score and using clinically relevant cutoffs (CC,≥1 and≥10; HNSCC,≥1 and≥20; ESCC, TNBC, and UC,≥10). The agreement between the Bench- Mark platforms and PD-L1 IHC 22C3 pharmDx was assessed by intraclass correlation coefficient (ICC) and a contingency table for clinical interpretation. A total of 522 samples were evaluated for the pan-tumor analysis (CC, n = 77; ESCC, n = 80; HNSCC, n = 126; TNBC, n = 118, UC, n = 121). Most clinical interpretations of PD-L1 status were concordant between the BenchMark XT and PD-L1 IHC 22C3 pharmDx for all five tumor types with regard to negative percentage agreement (NPA; 83-97%), positive percentage agreement (PPA; 86- 100%), and overall percentage agreement (OPA; 90-97%); the ICC by tumor type was high (≥0.88). Importantly, the pan-tumor ICC was 0.95 (95% CI 0.94-0.96). Thirty additional TNBC samples were evaluated using the BenchMark ULTRA and PD-L1 IHC 22C3 pharmDx; the NPA, PPA, and OPA were 100%. The 22C3 antibody-based LDT on Ventana BenchMark XT and BenchMark ULTRA platforms demonstrated high concordance with the regulatory-approved PD-L1 IHC 22C3 pharmDx across multiple tumor types. These findings suggest the comparability of PD-L1 IHC 22C3 pharmDx with an LDT based on the 22C3 antibody.
AB - We conducted an analysis across multiple PD-L1 combined positive score (CPS) indications to establish concordance of a 22C3 antibody-based laboratory-developed test (LDT) on the Ventana BenchMark XT or BenchMark ULTRA platform and the regulatory-approved PD-L1 IHC 22C3 pharmDx in cervical cancer (CC), esophageal squamous cell carcinoma (ESCC), head and neck squamous cell carcinoma (HNSCC), triple-negative breast cancer (TNBC), and urothelial carcinoma (UC). Tumor specimens from each tumor type were stained with 22C3 antibody and scored using the 22C3 antibody-based LDT, and scores were compared with those using PD-L1 IHC 22C3 pharmDx. PD-L1 status was measured by the pathologist using CPS as a continuous score and using clinically relevant cutoffs (CC,≥1 and≥10; HNSCC,≥1 and≥20; ESCC, TNBC, and UC,≥10). The agreement between the Bench- Mark platforms and PD-L1 IHC 22C3 pharmDx was assessed by intraclass correlation coefficient (ICC) and a contingency table for clinical interpretation. A total of 522 samples were evaluated for the pan-tumor analysis (CC, n = 77; ESCC, n = 80; HNSCC, n = 126; TNBC, n = 118, UC, n = 121). Most clinical interpretations of PD-L1 status were concordant between the BenchMark XT and PD-L1 IHC 22C3 pharmDx for all five tumor types with regard to negative percentage agreement (NPA; 83-97%), positive percentage agreement (PPA; 86- 100%), and overall percentage agreement (OPA; 90-97%); the ICC by tumor type was high (≥0.88). Importantly, the pan-tumor ICC was 0.95 (95% CI 0.94-0.96). Thirty additional TNBC samples were evaluated using the BenchMark ULTRA and PD-L1 IHC 22C3 pharmDx; the NPA, PPA, and OPA were 100%. The 22C3 antibody-based LDT on Ventana BenchMark XT and BenchMark ULTRA platforms demonstrated high concordance with the regulatory-approved PD-L1 IHC 22C3 pharmDx across multiple tumor types. These findings suggest the comparability of PD-L1 IHC 22C3 pharmDx with an LDT based on the 22C3 antibody.
UR - http://www.scopus.com/inward/record.url?scp=85160890947&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0285764
DO - 10.1371/journal.pone.0285764
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C2 - 37267266
AN - SCOPUS:85160890947
SN - 1932-6203
VL - 18
JO - PLoS ONE
JF - PLoS ONE
IS - 6 June
M1 - e0285764
ER -