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可切除非小细胞肺癌围手术期免疫治疗的临床结局

Clinical Outcomes of Perioperative Immunotherapy in Resectable Non-Small Cell Lung Cancer.

作者信息

Desai Aakash, Schwed Karen, Kalesinskas Laurynas, Yuan Qianyu, Bryan Jonathan, Keane Catherine, Fidyk Erin, Castellanos Emily, Cohen Aaron B, Harrison Katherine, Ho George, Marinescu Anca, Leal Ticiana A

机构信息

Division of Hematology and Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham.

Flatiron Health, New York, New York.

出版信息

JAMA Netw Open. 2025 Jun 2;8(6):e2517953. doi: 10.1001/jamanetworkopen.2025.17953.


DOI:10.1001/jamanetworkopen.2025.17953
PMID:40587130
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12210081/
Abstract

IMPORTANCE: Lung cancer remains a leading cause of cancer-related mortality, with early-stage non-small cell lung cancer (NSCLC) accounting for 40% to 45% of new diagnoses. Despite the adoption of perioperative chemoimmunotherapy, clinical data on its use and outcomes remain limited. OBJECTIVE: To evaluate clinical practice patterns and outcomes associated with neoadjuvant and adjuvant chemoimmunotherapy use in patients with resectable stage II to IIIA NSCLC. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study obtained data from the Flatiron Health database containing deidentified, patient-level, electronic health record-derived data from approximately 280 cancer clinics in the US. The cohort included adults diagnosed with stage II to IIIA NSCLC between January 1, 2020, and October 31, 2023, who underwent surgical resection. Included patients were receiving neoadjuvant chemoimmunotherapy (nivolumab or pembrolizumab with platinum-based doublet chemotherapy) or adjuvant chemoimmunotherapy (atezolizumab or pembrolizumab with or without chemotherapy) after the US Food and Drug Administration approval of these therapies. EXPOSURES: Neoadjuvant and adjuvant chemoimmunotherapy for resectable NSCLC. MAIN OUTCOMES AND MEASURES: The primary outcome was clinical distant metastasis-free survival (DMFS), defined as time from treatment initiation to distant metastasis or death. Secondary outcomes included biomarker testing rates, time to treatment, and metastatic patterns. RESULTS: Included in the analysis were 1334 patients with resectable stage II to IIIA NSCLC treated with immunotherapy, of whom 424 (median [IQR] age, 68 [63.0-74.0] years; 225 males [53.1%]) received chemoimmunotherapy with platinum-based doublet in the neoadjuvant setting and 910 (median [IQR] age, 69 [63.0-74.0] years; 441 males [48.5%]) received chemoimmunotherapy or immunotherapy alone in the adjuvant setting. The clinical DMFS at 18 months was 80.2% (95% CI, 75.0%-85.7%) for the neoadjuvant cohort and 83.0% (95% CI, 80.0%-86.0%) for the adjuvant cohort. Biomarker testing rates were higher in the adjuvant cohort compared to the neoadjuvant cohort (eg, programmed cell death ligand 1 testing: 72.2% vs 52.6%, P < .001). Common metastatic sites included brain, bone, and pleura, consistent across cohorts. Chemoimmunotherapy among patients who received surgery increased from 2022 to 2023 but remained under 30% of eligible patients (neoadjuvant setting: from 8.4% [82 of 966] to 13.8% [254 of 1842]; adjuvant setting: from 19.7% [372 of 1887] to 22.6% [401 of 1776]). CONCLUSIONS AND RELEVANCE: This retrospective cohort study found that chemoimmunotherapy was associated with favorable clinical DMFS outcomes in patients with resectable NSCLC. The findings highlight the need to address barriers to broader adoption of chemoimmunotherapy.

摘要

重要性:肺癌仍然是癌症相关死亡的主要原因,早期非小细胞肺癌(NSCLC)占新诊断病例的40%至45%。尽管采用了围手术期化疗免疫疗法,但其使用和疗效的临床数据仍然有限。 目的:评估可切除的II至IIIA期NSCLC患者新辅助和辅助化疗免疫疗法的临床实践模式及疗效。 设计、设置和参与者:这项回顾性队列研究从Flatiron Health数据库获取数据,该数据库包含来自美国约280家癌症诊所的匿名患者级电子健康记录衍生数据。该队列包括2020年1月1日至2023年10月31日期间被诊断为II至IIIA期NSCLC并接受手术切除的成年人。纳入的患者在美国食品药品监督管理局批准这些疗法后接受新辅助化疗免疫疗法(纳武单抗或帕博利珠单抗联合铂类双药化疗)或辅助化疗免疫疗法(阿特珠单抗或帕博利珠单抗联合或不联合化疗)。 暴露因素:可切除NSCLC的新辅助和辅助化疗免疫疗法。 主要结局和指标:主要结局是临床无远处转移生存期(DMFS),定义为从治疗开始到远处转移或死亡的时间。次要结局包括生物标志物检测率、治疗时间和转移模式。 结果:分析纳入了1334例接受免疫疗法治疗的可切除II至IIIA期NSCLC患者,其中424例(中位[IQR]年龄,68[63.0 - 74.0]岁;225例男性[53.1%])在新辅助治疗中接受铂类双药化疗免疫疗法,910例(中位[IQR]年龄,69[63.0 - 74.0]岁;441例男性[48.5%])在辅助治疗中接受化疗免疫疗法或单纯免疫疗法。新辅助队列18个月时的临床DMFS为80.2%(95%CI,75.0% - 85.7%),辅助队列18个月时的临床DMFS为83.0%(95%CI,80.0% - 86.0%)。辅助队列的生物标志物检测率高于新辅助队列(例如,程序性细胞死亡配体1检测:72.2%对52.6%,P < 0.001)。常见转移部位包括脑、骨和胸膜,各队列一致。接受手术的患者中化疗免疫疗法的使用从2022年到2023年有所增加,但仍低于 eligible 患者的30%(新辅助治疗:从8.4%[966例中的82例]增至13.8%[1842例中的254例];辅助治疗:从19.7%[1887例中的372例]增至22.6%[1776例中的401例])。 结论和相关性:这项回顾性队列研究发现,化疗免疫疗法与可切除NSCLC患者良好的临床DMFS结局相关。研究结果凸显了解决化疗免疫疗法更广泛应用障碍的必要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7f1/12210081/3f3fd52f6564/jamanetwopen-e2517953-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7f1/12210081/36adacd373a2/jamanetwopen-e2517953-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7f1/12210081/c07ae2e79b80/jamanetwopen-e2517953-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7f1/12210081/7e306f65f8f4/jamanetwopen-e2517953-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7f1/12210081/3f3fd52f6564/jamanetwopen-e2517953-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7f1/12210081/36adacd373a2/jamanetwopen-e2517953-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7f1/12210081/c07ae2e79b80/jamanetwopen-e2517953-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7f1/12210081/7e306f65f8f4/jamanetwopen-e2517953-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a7f1/12210081/3f3fd52f6564/jamanetwopen-e2517953-g004.jpg

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本文引用的文献

[1]
Neoadjuvant and Adjuvant Treatments for Early Stage Resectable NSCLC: Consensus Recommendations From the International Association for the Study of Lung Cancer.

J Thorac Oncol. 2024-10

[2]
Relationships between survival and real-world recurrence-free survival or distant metastasis-free survival among patients with completely resected stage IIB or IIC melanoma.

Melanoma Res. 2024-8-1

[3]
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N Engl J Med. 2024-4-11

[4]
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JAMA Oncol. 2024-5-1

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[6]
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Ann Thorac Surg. 2024-9

[7]
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N Engl J Med. 2023-11-2

[8]
Approach to machine learning for extraction of real-world data variables from electronic health records.

Front Pharmacol. 2023-9-15

[9]
Perioperative Pembrolizumab for Early-Stage Non-Small-Cell Lung Cancer.

N Engl J Med. 2023-8-10

[10]
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CA Cancer J Clin. 2023-1

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