Pathologist reproducibility of combined positive score (CPS) for the evaluation of PD-L1 in gastric or gastroesophageal junction adenocarcinoma tumors

Background: The clinically relevant and highly reproducible combined positive score (CPS) algorithm is used in conjunction with PD-L1 IHC 22C3 pharmDx for evaluation of programmed death ligand 1 (PD-L1) expression in gastric or gastroesophageal junction (GEJ) adenocarcinoma specimens. PD-L1 IHC 22C3 pharmDx and the CPS algorithm were approved by the United States Food and Drug Administration (FDA) on September 22, 2017 to aid in identifying patients likely to respond to pembrolizumab. Objective: Assessment of pathologist reproducibility in the gastric and GEJ adenocarcinoma Early Validation Program (EVP). Methods: Immunohistochemical (IHC) staining for PD-L1 was performed on thirty gastric or GEJ adenocarcinoma surgical resection specimens with PD-L1 IHC 22C3 pharmDx. All specimens were evaluated by in-house pathologists and assigned a reference CPS. Inter-pathologist and intra-pathologist reproducibility was assessed in ten pathologists from five clinical labs. Acceptance criteria was based on a minimum of 85% agreement with the reference CPS. Results: Nine pathologists met acceptance criteria for inter-observer reproducibility (87-100% agreement) and intra-observer reproducibility (87-100% agreement). One pathologist had 90% inter-pathologist agreement and 80% intra-pathologist agreement. This pathologist received additional training and achieved 87% intra-pathologist agreement upon re-testing. Upon completion of EVP, all ten participating pathologists were certified to score gastric or GEJ adenocarcinoma specimens stained with PD-L1 IHC 22C3 pharmDx. Inter-pathologist (87.6% overall agreement) and intra-pathologist (93% overall agreement) studies performed in analytical validation demonstrate similar reproducibility. Conclusion: The CPS algorithm is highly reproducible within and among pathologists for gastric or GEJ adenocarcinoma specimens stained with PD-L1 IHC 22C3 pharmDx, as demonstrated in analytical validation. Citation Format: Lindsay Guerrero, Karina Kulangara, Yen Truong, Sue Schwefel, Debra Hanks. Pathologist reproducibility of combined positive score (CPS) for the evaluation of PD-L1 in gastric or gastroesophageal junction adenocarcinoma tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-218.