Gut Microbiota in Advanced Non-small-cell Lung Cancer Receiving Chemo-immunotherapy: An Ancillary Biomarker Study from the Phase III trial JCOG2007 (NIPPON).

IF 21 1区 医学 Q1 ONCOLOGY Journal of Thoracic Oncology Pub Date : 2025-03-07 DOI:10.1016/j.jtho.2025.02.026
Taiki Hakozaki, Kentaro Tanaka, Yoshimasa Shiraishi, Yuta Sekino, Noriko Mitome, Yusuke Okuma, Tomoiki Aiba, Takahiro Utsumi, Junko Tanizaki, Koichi Azuma, Satoshi Hara, Ryo Morita, Seiji Niho, Toshihide Yokoyama, Ryo Toyozawa, Hidehito Horinouchi, Isamu Okamoto, Yukio Hosomi, Yuichiro Ohe
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引用次数: 0

Abstract

Background: Immunotherapy has transformed treatment for non-small cell lung cancer (NSCLC). However, reliable biomarkers for treatment selection remain scarce. Gut microbiota has emerged as a potential biomarker, but its role in chemo-immunotherapy for NSCLC is unclear.

Methods: The phase III trial (JCOG2007, NIPPON) compared pembrolizumab plus platinum doublet chemotherapy (PC) and nivolumab-ipilimumab plus platinum doublet chemotherapy (NIC) in treatment-naïve advanced NSCLC patients without driver gene alterations. As an ancillary biomarker study, 270 patients with baseline fecal samples were analyzed for gut microbiota composition out of 295 patients enrolled. 16S rDNA sequencing was performed for the diversity and differential abundance analysis.

Results: The beta diversity analysis of the overall cohort (n=270) revealed distinct microbial structures between the subpopulations defined by whether overall survival (OS) exceeds 12 or 18 months. Subsequent LEfSe analysis identified specific bacterial genera that differed between the subpopulations, with Fusicatenibacter, Butyricicoccus, and Blautia being enriched in patients with longer OS. Regarding adverse events (AEs), lower microbial alpha diversity and the presence of certain taxa were linked to a higher risk of serious (≥ Grade 4) AEs. Additionally, favorable genera, including Fusicatenibacter and Butyricicoccus, were associated with a lower risk of serious AEs. Lastly, regimen-specific analysis showed that higher abundance of Fusicatenibacter and Butyricicoccus were linked to better OS in the NIC arm compared to that in the CP arm (Hazard Ratio (HR) for OS = 0.56 and 0.52, respectively). Conversely, the higher abundance of Prevotellaceae NK3B31 was associated with higher mortality risk in the NIC arm (HR for OS = 2.33).

Conclusions: Gut microbiota may serve as a biomarker for chemo-immunotherapy in advanced NSCLC. Differences in microbial diversity and specific bacterial genera were associated with prognosis and serious AEs, with potential regimen-specific effects. These findings support integrating gut microbiota profiling into clinical practice to optimize first-line treatment strategies.

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来源期刊
Journal of Thoracic Oncology
Journal of Thoracic Oncology 医学-呼吸系统
CiteScore
36.00
自引率
3.90%
发文量
1406
审稿时长
13 days
期刊介绍: Journal of Thoracic Oncology (JTO), the official journal of the International Association for the Study of Lung Cancer,is the primary educational and informational publication for topics relevant to the prevention, detection, diagnosis, and treatment of all thoracic malignancies.The readship includes epidemiologists, medical oncologists, radiation oncologists, thoracic surgeons, pulmonologists, radiologists, pathologists, nuclear medicine physicians, and research scientists with a special interest in thoracic oncology.
期刊最新文献
Gut Microbiota in Advanced Non-small-cell Lung Cancer Receiving Chemo-immunotherapy: An Ancillary Biomarker Study from the Phase III trial JCOG2007 (NIPPON). Selective depletion of CCR8+Treg cells enhances anti-tumor immunity of cytotoxic T cells in lung cancer via dendritic cells. Erratum In this issue Editorial Board
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