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

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

Publication Date

11-1-2023

Journal

Clinical Cancer Research

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.

Keywords

Humans, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Immune Checkpoint Inhibitors, B7-H1 Antigen, Retrospective Studies, Antineoplastic Agents, Immunological, Biomarkers, Tumor

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Supplementary Materials

PMID: 37432985