Clinical and molecular correlates of PD-L1 expression in patients with lung adenocarcinomas Journal Article


Authors: Schoenfeld, A. J.; Rizvi, H.; Bandlamudi, C.; Sauter, J. L.; Travis, W. D.; Rekhtman, N.; Plodkowski, A. J.; Perez-Johnston, R.; Sawan, P.; Beras, A.; Egger, J. V.; Ladanyi, M.; Arbour, K. C.; Rudin, C. M.; Riely, G. J.; Taylor, B. S.; Donoghue, M. T. A.; Hellmann, M. D.
Article Title: Clinical and molecular correlates of PD-L1 expression in patients with lung adenocarcinomas
Abstract: Background: Programmed death-ligand 1 (PD-L1) expression is the only FDA-approved biomarker for immune checkpoint inhibitors (ICIs) in patients with lung adenocarcinoma, but sensitivity is modest. Understanding the impact of molecular phenotype, clinical characteristics, and tumor features on PD-L1 expression is largely unknown and may improve prediction of response to ICI. Patients and methods: We evaluated patients with lung adenocarcinoma for whom PD-L1 testing and targeted next-generation sequencing (using MSK-IMPACT) was performed on the same tissue sample. Clinical and molecular features were compared across PD-L1 subgroups to examine how molecular phenotype associated with tumor PD-L1 expression. In patients treated with anti-PD-(L)1 blockade, we assessed how these interactions impacted efficacy. Results: A total of 1586 patients with lung adenocarcinoma had paired PD-L1 testing and targeted next-generation sequencing. PD-L1 negativity was more common in primary compared to metastatic samples (P < 0.001). The distribution of PD-L1 expression (lymph nodes enriched for PD-L1 high; bones predominantly PD-L1 negative) and predictiveness of PD-L1 expression on ICI response varied by organ. Mutations in KRAS, TP53, and MET significantly associated with PD-L1 high expression (each P < 0.001, Q < 0.001) and EGFR and STK11 mutations associated with PD-L1 negativity (P < 0.001, Q = 0.01; P = 0.001, Q < 0.001, respectively). WNT pathway alterations also associated with PD-L1 negativity (P = 0.005). EGFR and STK11 mutants abrogated the predictive value of PD-L1 expression on ICI response. Conclusion: PD-L1 expression and association with ICI response vary across tissue sample sites. Specific molecular features are associated with differential expression of PD-L1 and may impact the predictive capacity of PD-L1 for response to ICIs. © 2020 European Society for Medical Oncology
Keywords: adult; controlled study; protein expression; aged; primary tumor; gene mutation; major clinical study; cancer patient; phenotype; vasculotropin receptor; metastasis; cohort analysis; tumor marker; tumor suppressor gene; lung adenocarcinoma; immunotherapy; lymph node; bone; egfr gene; oncogene k ras; wnt protein; predictive value; scatter factor receptor; pd-1; programmed death 1 ligand 1; nsclc; wnt signaling; pd-l1; protein kinase lkb1; met gene; cancer prognosis; high throughput sequencing; human; male; female; priority journal; article; stk11 gene
Journal Title: Annals of Oncology
Volume: 31
Issue: 5
ISSN: 0923-7534
Publisher: Oxford University Press  
Date Published: 2020-05-01
Start Page: 599
End Page: 608
Language: English
DOI: 10.1016/j.annonc.2020.01.065
PUBMED: 32178965
PROVIDER: scopus
DOI/URL:
Notes: Article -- Source: Scopus
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MSK Authors
  1. Natasha Rekhtman
    278 Rekhtman
  2. Marc Ladanyi
    1043 Ladanyi
  3. William D Travis
    606 Travis
  4. Gregory J Riely
    417 Riely
  5. Matthew David Hellmann
    255 Hellmann
  6. Barry Stephen Taylor
    191 Taylor
  7. Charles Rudin
    229 Rudin
  8. Kathryn Cecilia Arbour
    33 Arbour
  9. Hira Abbas Rizvi
    44 Rizvi
  10. Peter Sawan
    10 Sawan
  11. Jennifer Lynn Sauter
    50 Sauter
  12. Amanda Marie Beras
    9 Beras
  13. Jacklynn V Egger
    5 Egger