Comparability of laboratory-developed and commercial PD-L1 assays in non-small cell lung carcinoma

Abstract

PD-L1 expression in non-small cell lung cancer (NSCLC) is predictive of response to treatment with PD-1 and PD-L1 inhibitors. Different inhibitors have been developed with different PD-L1 assays, which use different PD-1 antibody clones on different immunohistochemistry platforms. Depending on instrument and reagent availability, laboratory-developed tests with cross-platform use of PD-L1 antibodies may have practical benefits over commercial assays. The 22C3 pharmDx Assay (referred to as 22C3 DAKO), the VENTANA PD-L1 SP263 Assay (referred to as SP263 VENTANA) and a lab-developed test using the 22C3 antibody on the VENTANA BenchMark ULTRA IHC/ISH system (referred to as 22C3 VENTANA) were performed on whole sections of 85 NSCLC surgical resections. All sections were independently scored by three pathologists using tumor proportion scores. Correlation coefficients for continuous scores in pairwise comparisons between assays ranged from 0.976 to 0.978. When using a 1% positivity threshold (dichotomous scores), the 22C3 DAKO assay and 22C3 VENTANA assays showed the greatest agreement (93% agreement, κ = 0.86, 95% CI 0.75–0.97), and the 22C3 DAKO and SP263 VENTANA assays tended to show slightly less agreement (84% agreement, κ = 0.66, 95% CI 0.50–0.82). When using a 50% positivity threshold (dichotomous scores), all pairwise comparisons showed similar agreement (96–99% agreement, κ = 0.89–0.97). Overall, there was no significant difference between assays at 1% or 50% thresholds (P = .77). These data are consistent with potential interchangeability of these assays, which may widen the scope of PD-L1 assays available to laboratories and reduce logistical barriers to testing.