Clinical and Molecular Features of Long-term Response to Immune Checkpoint Inhibitors in Patients with Advanced Non-Small Cell Lung Cancer.

Abstract

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.

• Authors: Rohit Thummalapalli, Biagio Ricciuti, Chaitanya Bandlamudi, Daniel Muldoon, Hira Rizvi, Arielle Elkrief, Jia Luo, Joao V Alessi, Federica Pecci, Giuseppe Lamberti, Alessandro Di Federico, Lingzhi Hong, Jianjun Zhang, John V Heymach, Don L Gibbons, Andrew J Plodkowski, Vignesh Ravichandran, Mark T A Donoghue, Chad Vanderbilt, Marc Ladanyi, Charles M Rudin, Mark G Kris, Gregory J Riely, Jamie E Chaft, Matthew D Hellmann, Natalie I Vokes, Mark M Awad, Adam J Schoenfeld
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 29 Issue 21 Pg. 4408-4418 (11 01 2023) ISSN: 1557-3265 [Electronic] United States
• PMID: 37432985 (Publication Type: Multicenter Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural)
• Copyright: ©2023 The Authors; Published by the American Association for Cancer Research.

Chemical References

• Immune Checkpoint Inhibitors
• B7-H1 Antigen
• Antineoplastic Agents, Immunological
• Biomarkers, Tumor

Topics

• Humans
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics, pathology)
• Lung Neoplasms (drug therapy, genetics, pathology)
• Immune Checkpoint Inhibitors (therapeutic use)
• B7-H1 Antigen
• Retrospective Studies
• Antineoplastic Agents, Immunological (adverse effects)
• Biomarkers, Tumor (genetics, therapeutic use)