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

Joao V. Alessi, Biagio Ricciuti, Xinan Wang, Federica Pecci, Alessandro Di Federico, Giuseppe Lamberti, Arielle Elkrief, Scott J. Rodig, Emily S. Lebow, Jordan E. Eicholz, Maria Thor, Andreas Rimner, Adam J. Schoenfeld, Jamie E. Chaft, Bruce E. Johnson, Daniel R. Gomez, Mark M. Awad and Narek Shaverdian ()
Additional contact information
Joao V. Alessi: Dana-Farber Cancer Institute
Biagio Ricciuti: Dana-Farber Cancer Institute
Xinan Wang: Harvard University
Federica Pecci: Dana-Farber Cancer Institute
Alessandro Di Federico: Dana-Farber Cancer Institute
Giuseppe Lamberti: Dana-Farber Cancer Institute
Arielle Elkrief: Memorial Sloan Kettering Cancer Center
Scott J. Rodig: Brigham and Women’s Hospital
Emily S. Lebow: Memorial Sloan Kettering Cancer Center
Jordan E. Eicholz: Memorial Sloan Kettering Cancer Center
Maria Thor: Memorial Sloan Kettering Cancer Center
Andreas Rimner: Memorial Sloan Kettering Cancer Center
Adam J. Schoenfeld: Memorial Sloan Kettering Cancer Center
Jamie E. Chaft: Memorial Sloan Kettering Cancer Center
Bruce E. Johnson: Dana-Farber Cancer Institute
Daniel R. Gomez: Memorial Sloan Kettering Cancer Center
Mark M. Awad: Dana-Farber Cancer Institute
Narek Shaverdian: Memorial Sloan Kettering Cancer Center

Nature Communications, 2023, vol. 14, issue 1, 1-12

Abstract: 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 (

Date: 2023
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DOI: 10.1038/s41467-023-39874-8

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