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Supplementary Figure S12 from Clinical and Molecular Features of Long-term Response to Immune Checkpoint Inhibitors in Patients with Advanced Non–Small Cell Lung Cancer

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posted on 2023-11-01, 07:21 authored by 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

Genomic features of patients with long-term response (LTR) compared to short term response (STR), non-LTR, and progressive disease (PD) among patients with TMB z-score ≥ 0.

Funding

National Institutes of Health (NIH)

Conquer Cancer Foundation (CCF)

Society for Immunotherapy of Cancer (SITC)

Mark Foundation For Cancer Research (The Mark Foundation for Cancer Research)

American Society of Clinical Oncology (ASCO)

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ARTICLE ABSTRACT

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). 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. 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. 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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cancer

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