Technical validation of PD-L1 SP142 assay for TNBC in a large academic center: Unexpected challenges.

Abstract

e15253 Background: The IMpassion 130 trial reported that 41-46% of TNBC are positive for PD-L1 SP142 based on centralized testing. While the FDA approved it as a companion diagnostic assay with cut off value of 1%, there are no published guidelines for technical validation in local laboratories. Furthermore, with the need to evaluate staining only in inflammatory cells (IC) the readout becomes particularly challenging for cases around the cutoff point. We report our prevalence of PD-L1 positivity and proportion of borderline cases in our validation. Methods: We ran PDL1 SP142 using the recommended protocol from Roche on the following groups: G1 - 53 consecutive TNBC cases (excisions tumors ≥7mm), G2 - 10 consecutive TNBC cases (breast specimens only) that would have met the inclusion criteria for the trial (LABC with poor NAT response or metastatic), G3 – proficiency testing slide from an EQA provider (4 cores of TNBC 1 negative, 1 borderline low positive and 2 high positive). All cases were read by 2 breast pathologists that received training on PDL1 readout by Roche (one – in class and online, one – online). Results: Borderline staining around the 1% cutoff (11 of 63) and low positive (9 of 63) were encountered in the validation sets more often than shown in training sessions. Classification of borderline cases may have a substantial impact on the rate of PDL1 positivity that potentially could approach 75%. Borderline cases often have IC staining either at the advancing tumor edge, as small collections of highly positive IC or around benign ducts entrapped within the tumor. Conclusions: The prevalence of PDL1 positive TNBC in all comers could be higher than observed in IMpassion 130 (at least 50-60%). Pathologist training in readout is of utmost importance due to high rate of borderline/low positive cases raising the need for central testing in borderline cases. Guideline recommendations for technical validation similar to other class II biomarkers would be useful. Studies on interobserver variability are needed to further address this potential issue. [Table: see text]