RT Journal Article
SR Electronic
T1 Automated image analysis of NSCLC biopsies to predict response to anti-PD-L1 therapy
JF Journal for ImmunoTherapy of Cancer
JO J Immunother Cancer
FD BMJ Publishing Group Ltd
SP 121
DO 10.1186/s40425-019-0589-x
VO 7
IS 1
A1 Sonja Althammer
A1 Tze Heng Tan
A1 Andreas Spitzmüller
A1 Lorenz Rognoni
A1 Tobias Wiestler
A1 Thomas Herz
A1 Moritz Widmaier
A1 Marlon C. Rebelatto
A1 Helene Kaplon
A1 Diane Damotte
A1 Marco Alifano
A1 Scott A. Hammond
A1 Marie-Caroline Dieu-Nosjean
A1 Koustubh Ranade
A1 Guenter Schmidt
A1 Brandon W. Higgs
A1 Keith E. Steele
YR 2019
UL http://jitc.bmj.com/content/7/1/121.abstract
AB Background Immune checkpoint therapies (ICTs) targeting the programmed cell death-1 (PD1)/programmed cell death ligand-1 (PD-L1) pathway have improved outcomes for patients with non-small cell lung cancer (NSCLC), particularly those with high PD-L1 expression. However, the predictive value of manual PD-L1 scoring is imperfect and alternative measures are needed. We report an automated image analysis solution to determine the predictive and prognostic values of the product of PD-L1+ cell and CD8+ tumor infiltrating lymphocyte (TIL) densities (CD8xPD-L1 signature) in baseline tumor biopsies.Methods Archival or fresh tumor biopsies were analyzed for PD-L1 and CD8 expression by immunohistochemistry. Samples were collected from 163 patients in Study 1108/NCT01693562, a Phase 1/2 trial to evaluate durvalumab across multiple tumor types, including NSCLC, and a separate cohort of 199 non-ICT- patients. Digital images were automatically scored for PD-L1+ and CD8+ cell densities using customized algorithms applied with Developer XD™ 2.7 software.Results For patients who received durvalumab, median overall survival (OS) was 21.0 months for CD8xPD-L1 signature-positive patients and 7.8 months for signature-negative patients (p = 0.00002). The CD8xPD-L1 signature provided greater stratification of OS than high densities of CD8+ cells, high densities of PD-L1+ cells, or manually assessed tumor cell PD-L1 expression ≥25%. The CD8xPD-L1 signature did not stratify OS in non-ICT patients, although a high density of CD8+ cells was associated with higher median OS (high: 67 months; low: 39.5 months, p = 0.0009) in this group.Conclusions An automated CD8xPD-L1 signature may help to identify NSCLC patients with improved response to durvalumab therapy. Our data also support the prognostic value of CD8+ TILS in NSCLC patients who do not receive ICT.Trial registration ClinicalTrials.gov identifier: NCT01693562.Study code: CD-ON-MEDI4736-1108.Interventional study (ongoing but not currently recruiting).Actual study start date: August 29, 2012.Primary completion date: June 23, 2017 (final data collection date for primary outcome measure).Abbreviations:ANOVAAnalysis of varianceCD8Cluster of differentiation 8CIConfidence intervalICTImmune checkpoint therapyIHCImmunohistochemistryNRNot reachedNSCLCNon-small cell lung cancerORRObjective response rateOSOverall survivalPD1Programmed cell death-1PD-L1Programmed cell death ligand-1PFSProgression-free survivalPPVPositive predictive valueRECISTResponse Evaluation Criteria in Solid TumorsTCTumor cellTILTumor infiltrating lymphocyteTMBTumor mutational burden