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Research ArticleClinical Studies

Dual Biomarker Combining DNA Damage Repair Gene Mutations and PD-L1 Expression for Immune Checkpoint Inhibitors in Non-small Cell Lung Cancer

HYERA KIM, DONG HYUN LIM, YONG SHIK KWON, MI AE KIM and KEON UK PARK
Anticancer Research May 2023, 43 (5) 2343-2349; DOI: https://doi.org/10.21873/anticanres.16399
HYERA KIM
1Division of Hematology-Oncology, Department of Internal Medicine, Keimyung University Dongsan Hospital, Keimyung University College of Medicine, Daegu, Republic of Korea;
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DONG HYUN LIM
2Department of Internal Medicine, Keimyung University Dongsan Hospital, Keimyung University College of Medicine, Daegu, Republic of Korea;
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YONG SHIK KWON
3Division of Pulmonology, Department of Internal Medicine, Keimyung University Dongsan Hospital, Keimyung University College of Medicine, Daegu, Republic of Korea
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MI AE KIM
3Division of Pulmonology, Department of Internal Medicine, Keimyung University Dongsan Hospital, Keimyung University College of Medicine, Daegu, Republic of Korea
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KEON UK PARK
1Division of Hematology-Oncology, Department of Internal Medicine, Keimyung University Dongsan Hospital, Keimyung University College of Medicine, Daegu, Republic of Korea;
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  • For correspondence: keonukpark@gmail.com
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Abstract

Background/Aim: Immune checkpoint inhibitors (ICIs) improve long-term survival in advanced non-small cell lung cancer (NSCLC) and require robust predictive biomarkers for the selection of responders. This study investigated the optimal implementation of DNA damage repair (DDR) gene mutations to predict response to ICIs in real-world NSCLC patients. Patients and Methods: We retrospectively reviewed 55 advanced NSCLC patients who had undergone targeted high-throughput sequencing and received ICIs. Patients with two or more DDR gene mutations were defined as DDR2 positive. Results: The patients’ median age was 68 (range=44-82) years, and 48 (87.3%) were men. Seventeen patients (30.9%) showed ≥50% high programmed death-ligand 1 (PD-L1) expression. Ten patients (18.2%) received an ICI-chemotherapy combination as first-line therapy, and 38 (69.1%) received ICI monotherapy as more than second-line therapy. Fourteen patients (25.5%) were DDR2-positive. The objective response rate of patients with DDR2-positive or PD-L1 ≥50% was 45.5%, and that of patients with DDR2-negative and PD-L1 <50% was 11.1% (p=0.007). In the PD-L1 low expression subgroup (<50%), patients with DDR2-positive had improved progression-free survival (PFS) and overall survival (OS) after ICIs compared to those with DDR2-negative (PFS: 5.8 vs. 1.9 months, p=0.026, OS: 14.4 vs. 7.2 months, p=0.078). DDR2-positive patients or those with PD-L1 ≥50% (24, 43.6%) had statistically significant improvement in PFS and OS after ICIs compared to DDR2-negative and those with PD-L1 <50% (PFS: 4.4 vs. 1.9 months, p=0.006, OS: 11.6 vs. 7.2 months, p=0.037). Conclusion: A dual biomarker combining DDR gene mutations and PD-L1 expression improves the prediction of response to ICIs in advanced NSCLC.

Key Words:
  • Non-small cell lung cancer
  • DNA damage repair
  • biomarker
  • immune checkpoint inhibitor
  • immunotherapy
  • Received February 14, 2023.
  • Revision received March 1, 2023.
  • Accepted March 2, 2023.
  • Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Anticancer Research: 43 (5)
Anticancer Research
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May 2023
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Dual Biomarker Combining DNA Damage Repair Gene Mutations and PD-L1 Expression for Immune Checkpoint Inhibitors in Non-small Cell Lung Cancer
HYERA KIM, DONG HYUN LIM, YONG SHIK KWON, MI AE KIM, KEON UK PARK
Anticancer Research May 2023, 43 (5) 2343-2349; DOI: 10.21873/anticanres.16399

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Dual Biomarker Combining DNA Damage Repair Gene Mutations and PD-L1 Expression for Immune Checkpoint Inhibitors in Non-small Cell Lung Cancer
HYERA KIM, DONG HYUN LIM, YONG SHIK KWON, MI AE KIM, KEON UK PARK
Anticancer Research May 2023, 43 (5) 2343-2349; DOI: 10.21873/anticanres.16399
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Keywords

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