TY - JOUR
T1 - Clinical and Molecular Features of Long-term Response to Immune Checkpoint Inhibitors in Patients with Advanced Non–Small Cell Lung Cancer
AU - Thummalapalli, Rohit
AU - Ricciuti, Biagio
AU - Bandlamudi, Chaitanya
AU - Muldoon, Daniel
AU - Rizvi, Hira
AU - Elkrief, Arielle
AU - Luo, Jia
AU - Alessi, Joao V.
AU - Pecci, Federica
AU - Lamberti, Giuseppe
AU - Di Federico, Alessandro
AU - Hong, Lingzhi
AU - Zhang, Jianjun
AU - Heymach, John V.
AU - Gibbons, Don L.
AU - Plodkowski, Andrew J.
AU - Ravichandran, Vignesh
AU - Donoghue, Mark T.A.
AU - Vanderbilt, Chad
AU - Ladanyi, Marc
AU - Rudin, Charles M.
AU - Kris, Mark G.
AU - Riely, Gregory J.
AU - Chaft, Jamie E.
AU - Hellmann, Matthew D.
AU - Vokes, Natalie I.
AU - Awad, Mark M.
AU - Schoenfeld, Adam J.
N1 - Publisher Copyright:
© 2023 The Authors; Published by the American Association for Cancer Research.
PY - 2023/11/1
Y1 - 2023/11/1
N2 - 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.
AB - 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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U2 - 10.1158/1078-0432.CCR-23-1207
DO - 10.1158/1078-0432.CCR-23-1207
M3 - Article
C2 - 37432985
AN - SCOPUS:85175741359
SN - 1078-0432
VL - 29
SP - 4408
EP - 4418
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 21
ER -