In a research article published in the journal Nature, Yale pathologists David Rimm, Emily Reisenbichler and colleagues investigated the PD-LI immunohistochemical assay, SP142, which recently received FDA approval. The assay is used as a companion test to determine eligibility for atezolizumab therapy in patients with advanced triple negative breast cancer (TNBC).
Researchers analyzed the assay performance to determine if the test could reproducibly determine treatment eligibility in TNBC patients, when scored by multiple observers and found serious discrepancies. Data in lung cancer studies also suggest this assay suffers from poor reproducibility.
The research team worked with 19 pathologists from 14 academic institutions to score PD-L1 staining of immune cells (IC) in TNBC sections stained with SP142 and SP263 assays. The research team utilized a new statistical method called ONEST or (Observers Needed to Evaluate Subjective Tests) which determines the “minimum number of evaluators needed to estimate concordance between large numbers of readers, as occurs in the real-world setting”.
The researchers concluded that the IC scoring with both assays showed poor reproducibility across multiple pathologists utilizing this ONEST analysis. This suggests over half of pathologists disagreed about the IC scores. As a result, the researchers concluded, many patients with TNBC may receive atezolizumab when they are unlikely to benefit, or not receive atezolizumab when they may benefit.