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Clinical and Molecular Features of Long-term Response to Immune Checkpoint Inhibitors in Patients with Advanced Non-Small Cell Lung Cancer.
Thummalapalli, Rohit; Ricciuti, Biagio; Bandlamudi, Chaitanya; Muldoon, Daniel; Rizvi, Hira; Elkrief, Arielle; Luo, Jia; Alessi, Joao V; Pecci, Federica; Lamberti, Giuseppe; Di Federico, Alessandro; Hong, Lingzhi; Zhang, Jianjun; Heymach, John V; Gibbons, Don L; Plodkowski, Andrew J; Ravichandran, Vignesh; Donoghue, Mark T A; Vanderbilt, Chad; Ladanyi, Marc; Rudin, Charles M; Kris, Mark G; Riely, Gregory J; Chaft, Jamie E; Hellmann, Matthew D; Vokes, Natalie I; Awad, Mark M; Schoenfeld, Adam J.
Afiliación
  • Thummalapalli R; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Ricciuti B; Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Bandlamudi C; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Muldoon D; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Rizvi H; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Elkrief A; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Luo J; Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Alessi JV; Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Pecci F; Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Lamberti G; Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Di Federico A; Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Hong L; Department of Thoracic/Head and Neck Medical Oncology, MD Anderson Cancer Center, Houston, Texas.
  • Zhang J; Department of Thoracic/Head and Neck Medical Oncology, MD Anderson Cancer Center, Houston, Texas.
  • Heymach JV; Department of Thoracic/Head and Neck Medical Oncology, MD Anderson Cancer Center, Houston, Texas.
  • Gibbons DL; Department of Thoracic/Head and Neck Medical Oncology, MD Anderson Cancer Center, Houston, Texas.
  • Plodkowski AJ; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Ravichandran V; Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Donoghue MTA; Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Vanderbilt C; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Ladanyi M; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Rudin CM; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Kris MG; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Riely GJ; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Chaft JE; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Hellmann MD; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Vokes NI; Department of Thoracic/Head and Neck Medical Oncology, MD Anderson Cancer Center, Houston, Texas.
  • Awad MM; Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Schoenfeld AJ; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Clin Cancer Res ; 29(21): 4408-4418, 2023 11 01.
Article en En | MEDLINE | ID: mdl-37432985
PURPOSE: We sought to identify features of patients with advanced non-small cell lung cancer (NSCLC) who achieve long-term response (LTR) to immune checkpoint inhibitors (ICI), and how these might differ from features predictive of short-term response (STR). EXPERIMENTAL DESIGN: We performed a multicenter retrospective analysis of patients with advanced NSCLC treated with ICIs between 2011 and 2022. LTR and STR were defined as response ≥ 24 months and response < 12 months, respectively. Tumor programmed death ligand 1 (PD-L1) expression, tumor mutational burden (TMB), next-generation sequencing (NGS), and whole-exome sequencing (WES) data were analyzed to identify characteristics enriched in patients achieving LTR compared with STR and non-LTR. RESULTS: Among 3,118 patients, 8% achieved LTR and 7% achieved STR, with 5-year overall survival (OS) of 81% and 18% among LTR and STR patients, respectively. High TMB (≥50th percentile) enriched for LTR compared with STR (P = 0.001) and non-LTR (P < 0.001). Whereas PD-L1 ≥ 50% enriched for LTR compared with non-LTR (P < 0.001), PD-L1 ≥ 50% did not enrich for LTR compared with STR (P = 0.181). Nonsquamous histology (P = 0.040) and increasing depth of response [median best overall response (BOR) -65% vs. -46%, P < 0.001] also associated with LTR compared with STR; no individual genomic alterations were uniquely enriched among LTR patients. CONCLUSIONS: Among patients with advanced NSCLC treated with ICIs, distinct features including high TMB, nonsquamous histology, and depth of radiographic improvement distinguish patients poised to achieve LTR compared with initial response followed by progression, whereas high PD-L1 does not.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma de Pulmón de Células no Pequeñas / Antineoplásicos Inmunológicos / Neoplasias Pulmonares Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Clin Cancer Res Asunto de la revista: NEOPLASIAS Año: 2023 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma de Pulmón de Células no Pequeñas / Antineoplásicos Inmunológicos / Neoplasias Pulmonares Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Clin Cancer Res Asunto de la revista: NEOPLASIAS Año: 2023 Tipo del documento: Article Pais de publicación: Estados Unidos