Molecular classification and biomarkers of outcome with immunotherapy in extensive-stage small-cell lung cancer: analyses of the CASPIAN phase 3 study

  1. Xie, Mingchao
  2. Vuko, Miljenka
  3. Rodriguez-Canales, Jaime
  4. Zimmermann, Johannes
  5. Schick, Markus
  6. O’Brien, Cathy
  7. Paz-Ares, Luis
  8. Goldman, Jonathan W.
  9. Garassino, Marina Chiara
  10. Gay, Carl M.
  11. Heymach, John V.
  12. Jiang, Haiyi
  13. Barrett, J. Carl
  14. Stewart, Ross A.
  15. Lai, Zhongwu
  16. Byers, Lauren A.
  17. Rudin, Charles M.
  18. Shrestha, Yashaswi

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1000 Titel
  • Molecular classification and biomarkers of outcome with immunotherapy in extensive-stage small-cell lung cancer: analyses of the CASPIAN phase 3 study
1000 Autor/in
  1. Xie, Mingchao |
  2. Vuko, Miljenka |
  3. Rodriguez-Canales, Jaime |
  4. Zimmermann, Johannes |
  5. Schick, Markus |
  6. O’Brien, Cathy |
  7. Paz-Ares, Luis |
  8. Goldman, Jonathan W. |
  9. Garassino, Marina Chiara |
  10. Gay, Carl M. |
  11. Heymach, John V. |
  12. Jiang, Haiyi |
  13. Barrett, J. Carl |
  14. Stewart, Ross A. |
  15. Lai, Zhongwu |
  16. Byers, Lauren A. |
  17. Rudin, Charles M. |
  18. Shrestha, Yashaswi |
1000 Verlag BioMed Central
1000 Erscheinungsjahr 2024
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2024-05-30
1000 Erschienen in
1000 Quellenangabe
  • 23(1):115
1000 Copyrightjahr
  • 2024
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1186/s12943-024-02014-x |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11137956/ |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • <jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>We explored potential predictive biomarkers of immunotherapy response in patients with extensive-stage small-cell lung cancer (ES-SCLC) treated with durvalumab (D) + tremelimumab (T) + etoposide-platinum (EP), D + EP, or EP in the randomized phase 3 CASPIAN trial.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>805 treatment-naïve patients with ES-SCLC were randomized (1:1:1) to receive D + T + EP, D + EP, or EP. The primary endpoint was overall survival (OS). Patients were required to provide an archived tumor tissue block (or ≥ 15 newly cut unstained slides) at screening, if these samples existed. After assessment for programmed cell death ligand-1 expression and tissue tumor mutational burden, residual tissue was used for additional molecular profiling including by RNA sequencing and immunohistochemistry.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>In 182 patients with transcriptional molecular subtyping, OS with D ± T + EP was numerically highest in the SCLC-inflamed subtype (<jats:italic>n</jats:italic> = 10, median 24.0 months). Patients derived benefit from immunotherapy across subtypes; thus, additional biomarkers were investigated. OS benefit with D ± T + EP versus EP was greater with high versus low <jats:italic>CD8A</jats:italic> expression/CD8 cell density by immunohistochemistry, but with no additional benefit with D + T + EP versus D + EP. OS benefit with D + T + EP versus D + EP was associated with high expression of <jats:italic>CD4</jats:italic> (median 25.9 vs. 11.4 months) and antigen-presenting and processing machinery (25.9 vs. 14.6 months) and MHC I and II (23.6 vs. 17.3 months) gene signatures, and with higher MHC I expression by immunohistochemistry.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>These findings demonstrate the tumor microenvironment is important in mediating better outcomes with D ± T + EP in ES-SCLC, with canonical immune markers associated with hypothesized immunotherapy mechanisms of action defining patient subsets that respond to D ± T.</jats:p> </jats:sec><jats:sec> <jats:title>Trial registration</jats:title> <jats:p>ClinicalTrials.gov, NCT03043872.</jats:p> </jats:sec>
1000 Sacherschließung
lokal Biomarkers
lokal CTLA-4
lokal PD-L1
lokal Aged [MeSH]
lokal Antibodies, Monoclonal/therapeutic use [MeSH]
lokal T-cell inflamed signature
lokal Lung Neoplasms/genetics [MeSH]
lokal Small Cell Lung Carcinoma/mortality [MeSH]
lokal Small-cell lung cancer
lokal Neoplasm Staging [MeSH]
lokal Immunotherapy/methods [MeSH]
lokal SCLC subtypes
lokal Small Cell Lung Carcinoma/drug therapy [MeSH]
lokal Male [MeSH]
lokal Small Cell Lung Carcinoma/genetics [MeSH]
lokal Lung Neoplasms/immunology [MeSH]
lokal Small Cell Lung Carcinoma/pathology [MeSH]
lokal Biomarkers, Tumor [MeSH]
lokal Molecular subtyping
lokal Female [MeSH]
lokal Lung Neoplasms/mortality [MeSH]
lokal Lung Neoplasms/therapy [MeSH]
lokal Adult [MeSH]
lokal Humans [MeSH]
lokal Small Cell Lung Carcinoma/metabolism [MeSH]
lokal Treatment Outcome [MeSH]
lokal Gene expression profiling
lokal Middle Aged [MeSH]
lokal Antineoplastic Combined Chemotherapy Protocols/therapeutic use [MeSH]
lokal Small Cell Lung Carcinoma/therapy [MeSH]
lokal Antigen presentation machinery
lokal Research
lokal Antibodies, Monoclonal, Humanized/therapeutic use [MeSH]
lokal Prognosis [MeSH]
lokal Lung Neoplasms/pathology [MeSH]
lokal Lung Neoplasms/metabolism [MeSH]
lokal Small Cell Lung Carcinoma/immunology [MeSH]
lokal Lung Neoplasms/drug therapy [MeSH]
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1000 Erstellt am 2025-02-06T19:50:31.571+0100
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