Clinical Utility of the Combined Positive Score for Programmed Death Ligand-1 Expression and the Approval of Pembrolizumab for Treatment of Gastric Cancer.
Context.--Regulatory approval of pembrolizumab for treatment of gastric and gastroesophageal junction (G/GEJ) adenocarcinoma required a reproducible scoring method for use of programmed death ligand-1 (PD-L1) protein expression as a companion diagnostic to identify likely responders to therapy. Obje...
| Published in: | Archives of Pathology & Laboratory Medicine Vol. 143; no. 3; pp. 330 - 338 |
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| Main Authors: | , , , , , , , , , , , , , |
| Format: | equations & formulas pictorial research tables/charts Journal Article |
| Published: |
College of American Pathologists
Mar2019
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=135037028&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 135037028 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00039985 1FS jtl: Archives of Pathology & Laboratory Medicine issn: 00039985 maglogo: N pubinfo: dt: Mar2019 vid: 143 iid: 3 pid: 2550 pub: College of American Pathologists place: Northfield, Illinois artinfo: ui: 135037028 135037028 135037028 10.5858/arpa.2018-0043-OA 135037028 ppf: 330 ppct: 8 formats: fmt: @attributes: type: P tig: atl: Clinical Utility of the Combined Positive Score for Programmed Death Ligand-1 Expression and the Approval of Pembrolizumab for Treatment of Gastric Cancer. aug: au: Kulangara, Karina Zhang, Nancy Corigliano, Ellie Guerrero, Lindsay Waldroup, Stephanie Jaiswal, Dipeshkumar Jansson, Malinka Shah, Supriya Hanks, Debra Jiangdian Wang Lunceford, Jared Savage, Mary J. Juco, Jonathan Emancipator, Kenneth affil: Division of Companion Diagnostics, Dako North America, Agilent Technologies, Carpinteria, California sug: subj: Stomach Neoplasms Drug Therapy Antibodies, Monoclonal Therapeutic Use Immunohistochemistry Antigens, Surface Gene Expression Human Antibodies, Monoclonal Immunology Algorithms Biological Markers Drug Approval Odds Ratio Confidence Intervals Prospective Studies ab: Context.--Regulatory approval of pembrolizumab for treatment of gastric and gastroesophageal junction (G/GEJ) adenocarcinoma required a reproducible scoring method for use of programmed death ligand-1 (PD-L1) protein expression as a companion diagnostic to identify likely responders to therapy. Objective.--To develop an immunohistochemical scoring algorithm that includes PD-L1 expression for tumor and immune cells, that is, the combined positive score. Design.--Four previously treated tumor types in the KEYNOTE-012 and KEYNOTE-028 studies were analyzed descriptively with a version of the PD-L1 immunohistochemical 22C3 pharmDx assay labeled for investigational use only to determine the relative importance of PD-L1 expression in tumor versus immune cells as a biomarker for pembrolizumab response. A combined positive score was developed as a novel scoring method and was compared with the tumor proportion score in cohort 1 from the KEYNOTE-059 study (G/GEJ cancer). External reproducibility was assessed. Results.--Per combined positive score cutoff of 1 or more, the prevalence of PD-L1 expression in patients with G/GEJ cancer was 57.6% (148 of 257 patients), with reasonable enrichment of responses (odds ratio, 2.8). Per tumor proportion score cutoff of 1% or more, prevalence was 12.5% (32 of 257 patients), with minimal enrichment (odds ratio, 1.4). External reproducibility assessments demonstrated interpathologist overall agreement of 96.6% (591 of 612; 95% CI, 94.0%--98.7%) and intrapathologist overall agreement of 97.2% (595 of 612; 95% CI, 95.3%--98.9%). Conclusions.--Combined positive score is a robust, reproducible PD-L1 scoring method that predicts response to pembrolizumab in patients with G/GEJ cancer. This novel scoring method supported US Food and Drug Administration approval of pembrolizumab as third-line therapy for G/GEJ cancer and has facilitated investigation in other indications. pubtype: Academic Journal doctype: equations & formulas pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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