Impact of TMB/PD-L1 expression and pneumonitis on chemoradiation and durvalumab response in stage III NSCLC Journal Article

   


Authors: Alessi, J. V.; Ricciuti, B.; Wang, X.; Pecci, F.; Di Federico, A.; Lamberti, G.; Elkrief, A.; Rodig, S. J.; Lebow, E. S.; Eicholz, J. E.; Thor, M.; Rimner, A.; Schoenfeld, A. J.; Chaft, J. E.; Johnson, B. E.; Gomez, D. R.; Awad, M. M.; Shaverdian, N.
Article Title: Impact of TMB/PD-L1 expression and pneumonitis on chemoradiation and durvalumab response in stage III NSCLC
Abstract: Although concurrent chemoradiation (CRT) and durvalumab consolidation has become a standard treatment for stage III non-small cell lung cancer (NSCLC), clinicopathologic and genomic factors associated with its efficacy remain poorly characterized. Here, in a multi-institutional retrospective cohort study of 328 patients treated with CRT and durvalumab, we identify that very high PD-L1 tumor proportion score (TPS) expression (≥ 90%) and increased tumor mutational burden (TMB) are independently associated with prolonged disease control. Additionally, we identify the impact of pneumonitis and its timing on disease outcomes among patients who discontinue durvalumab: compared to patients who experienced early-onset pneumonitis (< 3 months) leading to durvalumab discontinuation, patients with late-onset pneumonitis had a significantly longer PFS (12.7 months vs not reached; HR 0.24 [95% CI, 0.10 to 0.58]; P = 0.001) and overall survival (37.2 months vs not reached; HR 0.26 [95% CI, 0.09 to 0.79]; P = 0.017). These findings suggest that opportunities exist to improve outcomes in patients with lower PD-L1 and TMB levels, and those at highest risk for pneumonitis. © 2023, The Author(s).
Keywords: retrospective studies; genetics; chemotherapy; gene expression; carcinoma, non-small-cell lung; lung neoplasms; cohort analysis; retrospective study; pneumonia; lung tumor; tumor; programmed death 1 ligand 1; non small cell lung cancer; cancer; humans; human; durvalumab; b7-h1 antigen
Journal Title: Nature Communications
Volume: 14
ISSN: 2041-1723
Publisher: Nature Publishing Group  
Date Published: 2023-07-15
Start Page: 4238
Language: English
DOI: 10.1038/s41467-023-39874-8
PUBMED: 37454214
PROVIDER: scopus
PMCID: PMC10349822
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85164760617&doi=10.1038%2fs41467-023-39874-8&partnerID=40&md5=14ac69f5d0685a8ab38169147d5b239a
Notes: Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Narek Shaverdian -- MSK author Jordan Eichholz's last name is misspelled on original publication -- Source: Scopus
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MSK Authors
  1. Daniel R Gomez
    237 Gomez
  2. Jamie Erin Chaft
    289 Chaft
  3. Andreas Rimner
    524 Rimner
  4. Maria Elisabeth Thor
    149 Thor
  5. Adam Jacob Schoenfeld
    131 Schoenfeld
  6. Narek Shaverdian
    98 Shaverdian
  7. Emily Schapira Lebow
    49 Lebow
  8. Arielle Elkrief
    41 Elkrief
  9. Jordan Elliott Eichholz
    35 Eichholz
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