Pathology Training For Combined Positive Score Algorithm For The Assessment Of Pd-L1 In Human Cancer Tissues

Introduction: A pathologist training and testing procedure was developed for evaluating PD-L1 expression using the Combined Positive Score (CPS) algorithm, with effectiveness assessed by examining the results of scoring reproducibility studies. Background: The CPS algorithm was developed for the immunohistochemical evaluation of PD-L1 in cancer tissues. The CPS algorithm has been correlated at specific expression levels with response to pembrolizumab therapy, with FDA approvals for PD-L1 IHC 22C3 pharmDx for gastric or gastroesophageal junction adenocarcinoma, esophageal squamous cell carcinoma, cervical cancer, urothelial carcinoma, and head and neck squamous cell carcinoma. During validation of PD-L1 IHC 22C3 pharmDx, a CPS training and testing procedure was developed. CPS algorithm: CPS is the number of PD-L1 staining cells (tumor cells, lymphocytes, macrophages) divided by the total number of viable tumor cells, multiplied by 100. Although the result of the calculation can exceed 100, the maximum score is defined as CPS 100. Scoring Reproducibility Study Design: Three pathologists independently read a set of specimens three times, with a 14-day washout between reads. Scores are evaluated for inter- and intra-reader negative percent agreement (NPA), positive percent agreement (PPA) and overall percent agreement (OA) endpoints. Acceptance criteria for all endpoints is the achievement of a lower bound of a 95% confidence interval of 85% or greater. Training, Practice and Testing: The training includes information acquisition and a microscopic demonstration of cancer specimens. Understanding is verified by testing. Once completed, the pathologist practices scoring representative specimens then proceeds to testing. Testing consists of the trainee scoring a set of cancer specimens using the CPS algorithm. The test set is scored over two sessions to assess both accuracy, by comparing the results with reference scores, and consistency, by comparing the pathologist9s scores on a subset of specimens read twice. A pathologist must pass both assessments to be certified. Results: From 2016 to 2018, 17 scoring reproducibility studies were conducted, which included the cut-offs of CPS 1 (10), CPS 10 (5) and CPS 20 (2). Eight cancer types and one study with multiple rare indications were evaluated. 42 certified pathologists participated. Fourteen studies met all acceptance criteria. Two studies missed one endpoint, inter-reader PPA, and one study missed two endpoints, inter- and intra-reader NPA. Conclusions: The CPS training and certification procedure for PD-L1 evaluation was shown to be effective by the performance of 42 newly trained pathologists in scoring reproducibility studies. Acceptance criteria were met for all endpoints for 33 of 42 pathologists (79%), and for 39 of 42 pathologists (93%) for inter-reader and intra-reader reproducibility respectively. Citation Format: Judith Frederick, Lindsay Guerrero, Tiffany Evans, Joseph Barreto, Karina Kulangara. Pathology training for combined positive score algorithm for the assessment of PD-L1 in human cancer tissues [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 749.