Association of CD274 (PD-L1) Copy Number Changes with Immune Checkpoint Inhibitor Clinical Benefit in Non-Squamous Non-Small Cell Lung Cancer. Oncologist 2022 Sep 02;27(9):732-739
Date
05/23/2022Pubmed ID
35598202Pubmed Central ID
PMC9438920DOI
10.1093/oncolo/oyac096Scopus ID
2-s2.0-85137155218 (requires institutional sign-in at Scopus site) 4 CitationsAbstract
BACKGROUND: We sought to characterize response to immune checkpoint inhibitor (ICI) in non-squamous non-small cell lung cancer (NSCLC) across various CD274 copy number gain and loss thresholds and identify an optimal cutoff.
MATERIALS AND METHODS: A de-identified nationwide (US) real-world clinico-genomic database was leveraged to study 621 non-squamous NSCLC patients treated with ICI. All patients received second-line ICI monotherapy and underwent comprehensive genomic profiling as part of routine clinical care. Overall survival (OS) from start of ICI, for CD274 copy number gain and loss cohorts across varying copy number thresholds, were assessed.
RESULTS: Among the 621 patients, patients with a CD274 CN greater than or equal to specimen ploidy +2 (N = 29) had a significantly higher median (m) OS when compared with the rest of the cohort (N = 592; 16.1 [8.9-37.3] vs 8.6 [7.1-10.9] months, hazard ratio (HR) = 0.6 [0.4-1.0], P-value = .05). Patients with a CD274 copy number less than specimen ploidy (N = 299) trended toward a lower mOS when compared to the rest of the cohort (N = 322; 7.5 [5.9-11.3] vs 9.6 [7.9-12.8] months, HR = 0.9 [0.7-1.1], P-value = .3).
CONCLUSION: This work shows that CD274 copy number gains at varying thresholds predict different response to ICI blockade in non-squamous NSCLC. Considering these data, prospective clinical trials should further validate these findings, specifically in the context of PD-L1 IHC test results.
Author List
Murugesan K, Jin DX, Comment LA, Fabrizio D, Hegde PS, Elvin JA, Alexander B, Levy MA, Frampton GM, Montesion M, Roychowdhury S, Kurzrock R, Ross JS, Albacker LA, Huang RSPAuthor
Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
B7-H1 AntigenCarcinoma, Non-Small-Cell Lung
DNA Copy Number Variations
Humans
Lung Neoplasms
Prospective Studies