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Impact of TMB/PD-L1 expression and pneumonitis on chemoradiation and durvalumab response in stage III NSCLC.
Alessi, Joao V; Ricciuti, Biagio; Wang, Xinan; Pecci, Federica; Di Federico, Alessandro; Lamberti, Giuseppe; Elkrief, Arielle; Rodig, Scott J; Lebow, Emily S; Eicholz, Jordan E; Thor, Maria; Rimner, Andreas; Schoenfeld, Adam J; Chaft, Jamie E; Johnson, Bruce E; Gomez, Daniel R; Awad, Mark M; Shaverdian, Narek.
Afiliación
  • Alessi JV; Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Ricciuti B; Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Wang X; Department of Environmental Health, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.
  • Pecci F; Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Di Federico A; Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Lamberti G; Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Elkrief A; Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Rodig SJ; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Lebow ES; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, few York, NY, USA.
  • Eicholz JE; ImmunoProfile, Brigham and Women's Hospital, Boston, MA, USA.
  • Thor M; Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
  • Rimner A; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Schoenfeld AJ; Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Chaft JE; Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Johnson BE; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Gomez DR; Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Awad MM; Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Shaverdian N; Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Nat Commun ; 14(1): 4238, 2023 07 15.
Article en En | MEDLINE | ID: mdl-37454214
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neumonía / Carcinoma de Pulmón de Células no Pequeñas / Neoplasias Pulmonares Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neumonía / Carcinoma de Pulmón de Células no Pequeñas / Neoplasias Pulmonares Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido