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Treatment and outcomes of limited stage small cell lung cancer in the Canadian small cell lung cancer database (CASCADE) 加拿大小细胞肺癌数据库(CASCADE)中有限期小细胞肺癌的治疗和预后
IF 4.4 2区 医学 Q1 ONCOLOGY Pub Date : 2025-11-14 DOI: 10.1016/j.lungcan.2025.108840
William J. Phillips , Luna Jia Zhan , Deepro Chowdhury , Jeniszka Gill , Alexander Sun , Rebekah Rittberg , Victor Cohen , Amanda J.W. Gibson , Michael Yan , Daniel Liwski , Saritha Surapaneni , Marie Frederique D’Amours , Fabian P.S. Yu , YongJin Kim , Rana A. Qadeer , David E. Dawe , Jason Agulnik , Vishal Navani , Andrea S. Fung , Stephanie Snow , Sara Moore

Introduction

There have been minimal advances in the systemic treatment of limited stage small cell lung cancer (LS-SCLC) for decades. With the publication of the ADRIATIC trial, consolidation durvalumab is a new standard of care. This study evaluated real-world treatments and clinical outcomes prior to the era of immunotherapy for LS-SCLC.

Methods

The Canadian Small Cell Lung Cancer Database (CASCADE) is a Canadian multi-institutional federated database that includes patients with SCLC from 9 academic institutions. This analysis included patients with pathologically confirmed LS-SCLC treated curatively between January 2001 and December 2022. Baseline characteristics and treatment patterns were obtained from medical records and assessed descriptively. The primary outcome was overall survival (OS) assessed using Kaplan Meier (KM) methods. OS was also assessed among patients who received treatment eligible for participation in the ADRIATIC trial.

Results

A total of 1,024 patients were included. Median age was 66 years old and 52 % of patients were female. Concurrent chemoradiation therapy (cCRT) was the most common treatment modality (76 %), followed by surgery (11 %) and sequential CRT (10 %). Median OS was 24.9 months (95 % confidence interval [CI] = 23.4–27.4). Only 36 % of patients treated with cCRT received treatment meeting eligibility criteria for the ADRIATIC trial. The most common reason for ineligibility was due to the radiation therapy (RT) dose/schedule used. Median OS of eligible and ineligible patients was 30.3 months (95 % CI = 26.4–36.4) versus 21.7 months (95 % CI = 19.7–24.9).

Conclusions

Survival outcomes for LS-SCLC remain poor despite curative-intent multimodality treatment. Immunotherapy represents a promising advance but a high proportion of patients in the real-world receive treatment that was not represented in the ADRIATIC trial. Future work evaluating the outcomes of patients treated with immunotherapy is critical to assess its real-world impact.
几十年来,有限期小细胞肺癌(LS-SCLC)的全身治疗进展甚微。随着ADRIATIC试验的发表,巩固durvalumab成为一种新的治疗标准。本研究评估了免疫治疗时代之前LS-SCLC的实际治疗和临床结果。方法加拿大小细胞肺癌数据库(CASCADE)是一个加拿大多机构联合数据库,包括来自9个学术机构的SCLC患者。该分析包括2001年1月至2022年12月期间病理证实的LS-SCLC治愈患者。从医疗记录中获得基线特征和治疗模式,并进行描述性评估。主要终点是使用Kaplan Meier (KM)方法评估的总生存期(OS)。接受治疗的有资格参加亚得里亚海试验的患者也进行了OS评估。结果共纳入1024例患者。中位年龄66岁,52%的患者为女性。同步放化疗(cCRT)是最常见的治疗方式(76%),其次是手术(11%)和序贯CRT(10%)。中位OS为24.9个月(95%置信区间[CI] = 23.4-27.4)。在接受cCRT治疗的患者中,只有36%的患者接受了符合亚得里亚海试验资格标准的治疗。最常见的不合格原因是由于使用的放射治疗(RT)剂量/时间表。合格和不合格患者的中位OS分别为30.3个月(95% CI = 26.4-36.4)和21.7个月(95% CI = 19.7-24.9)。结论:尽管采用了多模式治疗,但LS-SCLC的生存结果仍然很差。免疫疗法代表了一个有希望的进步,但在现实世界中,有很大比例的患者接受了亚得里亚海试验中没有出现的治疗。未来评估患者免疫治疗结果的工作对于评估其实际影响至关重要。
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引用次数: 0
Genetic composition and evolutionary trajectories of brain metastasis in non-small-cell lung cancer 非小细胞肺癌脑转移的遗传组成和进化轨迹。
IF 4.4 2区 医学 Q1 ONCOLOGY Pub Date : 2025-11-14 DOI: 10.1016/j.lungcan.2025.108842
Marcin Nicoś , Natalia Galant , Anna Kowalczyk , Rafał Pęksa , Bożena Jarosz , Monika Żuk , Bartosz Wasąg , Renata Duchnowska , Paweł Krawczyk , Jacek Jassem , Nicola Crosetto

Introduction

Non-small cell lung cancer (NSCLC) is an aggressive solid malignancy that commonly disseminates to the central nervous system (CNS). Comparative analysis of primary NSCLC and brain metastases (BM) by next-generation sequencing may reveal somatic genetic alterations that drive or favor NSCLC-derived BM.

Methods

We performed whole-exome sequencing (WES) in 62 archival samples from 31 paired-matched primary NSCLC sites and corresponding BM. The median age of patients was 66 years; 22 had adenocarcinoma, and 9 had squamous cell carcinoma, 6 patients presented synchronous BM at lung cancer diagnosis, and 22 developed BM after 1–78 months (median 13 months).

Results

Mutations in the RTK-RAS, WNT, NOTCH, and PIK pathways were enriched across all samples. The KMT2D and TP53 genes were the most frequently mutated in the primary tumor and corresponding BM. FAT1, NSD1, and NF1 mutations were among the most frequent alterations newly detected in BM. Non-druggable hotspot alterations in actionable genes, including EGFR, KRAS, ALK, and ROS1, showed various patterns between the two tumor sites.

Conclusions

Our study provides a comprehensive overview of genetic alterations specific to primary NSCLC, unique to BM, and shared between both sites, which may contribute to BM formation affecting various evolutionary trajectories.
简介:非小细胞肺癌(NSCLC)是一种侵袭性实体恶性肿瘤,通常扩散到中枢神经系统(CNS)。通过下一代测序对原发性NSCLC和脑转移瘤(BM)的比较分析可能揭示驱动或促进NSCLC衍生的BM的体细胞遗传改变。方法:我们对来自31个配对的原发性NSCLC位点和相应BM的62个档案样本进行了全外显子组测序(WES)。患者年龄中位数为66岁;22例为腺癌,9例为鳞状细胞癌,6例在肺癌诊断时出现同步脑转移,22例在1-78个月(中位13个月)后发生脑转移。结果:RTK-RAS、WNT、NOTCH和PIK通路的突变在所有样本中都富集。KMT2D和TP53基因在原发肿瘤和相应的BM中最常发生突变。FAT1、NSD1和NF1突变是BM中新发现的最常见的突变。可操作基因(包括EGFR、KRAS、ALK和ROS1)的非药物热点改变在两个肿瘤部位之间表现出不同的模式。结论:我们的研究提供了原发性NSCLC特有的遗传改变的全面概述,这是BM特有的,并且在两个位点之间共享,这可能有助于BM的形成,影响各种进化轨迹。
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引用次数: 0
Impact of N1 lymph node burden on survival outcomes in non-skip pN2 non-small-cell lung cancer N1淋巴结负担对非跳跃pN2非小细胞肺癌生存结局的影响
IF 4.4 2区 医学 Q1 ONCOLOGY Pub Date : 2025-11-13 DOI: 10.1016/j.lungcan.2025.108839
Bin Luo , Shenhua Liang , Leqi Zhong , Wuyou Gao, Mingyue Zeng, Youfang Chen, Zhesheng Wen

Objectives

This study aimed to evaluate the prognostic value of quantitative N1 nodal burden metrics—including positive node count, positive station count, lymph node ratio (LNR), and lymph node station ratio (LNsR)—in patients with non-skip pN2 non-small cell lung cancer (NSCLC).

Methods

This retrospective study included 477 non-skip pN2 NSCLC patients who underwent complete surgical resection at our center from December 2008 to December 2020. N1 metrics were dichotomized based on optimal cutoffs determined by overall survival (OS). Kaplan-Meier analysis and Cox regression models were utilized to assess disease-free survival (DFS) and OS and to identify independent prognostic factors.

Results

In multivariable analysis, a high N1 LNR emerged as the sole N1 metric that independently predicted worse DFS (HR = 1.47, 95 % CI: 1.05–2.04, p = 0.023). In contrast, its prognostic significance for OS was attenuated (p = 0.162). However, an advanced pT4 stage (p = 0.044) was an independent predictor of worse OS, while adjuvant therapy (p = 0.016) was associated with improved OS. Notably, subgroup analysis revealed that an elevated N1 LNR independently predicted worse DFS in the pN2a subgroup (p = 0.009). Building on this, we developed a novel three-tiered stratification (pN2a-low LNR, pN2a-high LNR, and pN2b) that effectively discriminated patient outcomes for both DFS (p < 0.001) and OS (p < 0.01).

Conclusions

N1 LNR is a powerful and independent predictor of disease recurrence in non-skip pN2 NSCLC, outperforming other N1 metrics for predicting DFS. Incorporating N1 LNR into clinical assessments, particularly for pN2a patients, can enhance prognostic accuracy and potentially guide more personalized surveillance and treatment strategies.
目的本研究旨在评估定量N1淋巴结负担指标(包括阳性淋巴结计数、阳性淋巴结计数、淋巴结比例(LNR)和淋巴结比例(LNsR))在非跳跃性pN2非小细胞肺癌(NSCLC)患者中的预后价值。方法本回顾性研究纳入了2008年12月至2020年12月在我中心接受完整手术切除的477例非跳跃性pN2 NSCLC患者。根据总生存期(OS)确定的最佳截止值对N1个指标进行二分类。Kaplan-Meier分析和Cox回归模型用于评估无病生存期(DFS)和OS,并确定独立预后因素。结果在多变量分析中,高N1 LNR是唯一独立预测较差DFS的N1指标(HR = 1.47, 95% CI: 1.05 ~ 2.04, p = 0.023)。相比之下,其对OS的预后意义减弱(p = 0.162)。然而,pT4期晚期(p = 0.044)是较差OS的独立预测因子,而辅助治疗(p = 0.016)与改善OS相关。值得注意的是,亚组分析显示,N1 LNR升高独立预测pN2a亚组的DFS恶化(p = 0.009)。在此基础上,我们开发了一种新的三层分层(pn2a -低LNR, pn2a -高LNR和pN2b),可以有效地区分DFS (p < 0.001)和OS (p < 0.01)的患者结局。结论sn1 LNR是非跳跃型pN2 NSCLC疾病复发的独立预测因子,在预测DFS方面优于其他N1指标。将N1 LNR纳入临床评估,特别是对pN2a患者,可以提高预后准确性,并可能指导更个性化的监测和治疗策略。
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引用次数: 0
Threshold of adequate resection margin for sub-lobar resection in peripheral clinical stage IA1-2 non-small cell lung cancer with tumor spread through air spaces 周边临床分期IA1-2期非小细胞肺癌经空气间隙扩散行亚叶下切除的适切量阈值
IF 4.4 2区 医学 Q1 ONCOLOGY Pub Date : 2025-11-12 DOI: 10.1016/j.lungcan.2025.108838
Hanbo Pan , Hui Yin , Wanyu Li , Weicheng Kong , Jiaqi Zhang , Hang Chen , Zhen Ge , Yu Tian , Junwei Ning , Zhizhuo Dai , Weiyang Huang , Liang Fang , Min Zheng , Guomo Ruan , Zhongjie Chen , Ming Zhang , Xiaomin Niu , Jia Huang , Chengwei Zhou , Guodong Xu , Qingquan Luo

Objectives

Sub-lobar resection (SR) is an established treatment for peripheral clinical stage IA1-2 (cIA1-2) non-small cell lung cancer (NSCLC). However, it may fail to achieve complete resection and is associated with worse survival than lobar resection (LR) in spread through air spaces (STAS)+ populations. This study aims to define the threshold of an adequate SR margin that may yield survival outcomes comparable to LR in peripheral cIA1-2 STAS+ NSCLC.

Methods

Consecutive patients with peripheral cIA1-2 (consolidation-to-tumor ratio > 0.5) NSCLC who underwent surgery between 2010 and 2020 across seven high-volume institutions were retrospectively reviewed. Stabilized inverse probability of treatment weighting (IPTW) was applied to mitigate selection bias. The primary endpoint was overall survival (OS), and the secondary endpoint was recurrence-free survival (RFS).

Results

A total of 6,027 STAS+ and 15,994 STAS patients were included. IPTW analyses demonstrated that SR was associated with improved long-term outcomes in STAS populations, whereas LR provided superior outcomes in STAS+ populations. Greater resection margin length and higher margin-to-tumor ratio (MTR) were independently associated with improved OS and RFS in STAS+ but not in STAS patients undergoing SR. Among STAS+ patients undergoing SR, cut-point analysis identified threshold values of 2.5 cm for resection margin length and 1.7 for MTR, which were validated in an external multi-center cohort. These cutoff values remained effective in patients with pathological visceral pleural invasion, lymphovascular invasion, or nodal involvement, and in those undergoing either segmentectomy or wedge resection.

Conclusions

In peripheral cIA1-2 NSCLC, STAS status may modify the prognostic impact of both resection extent and margin. For STAS+ patients, an SR margin length of ≥2.5 cm or an MTR of ≥1.7 may be recommended to achieve oncologic outcomes comparable to LR.
目的亚肺叶切除术(SR)是治疗周围临床分期IA1-2 (cIA1-2)非小细胞肺癌(NSCLC)的一种成熟治疗方法。然而,在通过空气间隙(STAS)+扩散的人群中,它可能无法实现完全切除,并且与大叶切除(LR)相比生存率更差。本研究旨在确定足够的SR边缘阈值,该阈值可能产生与外周cIA1-2 STAS+ NSCLC中LR相当的生存结果。方法回顾性分析2010年至2020年7家大容量机构连续接受手术的外周cIA1-2(实变-肿瘤比>; 0.5) NSCLC患者。采用稳定处理加权逆概率(IPTW)来减轻选择偏差。主要终点是总生存期(OS),次要终点是无复发生存期(RFS)。结果共纳入STAS+患者6027例,STAS -患者15994例。IPTW分析表明,在STAS -人群中,SR与改善的长期预后有关,而在STAS+人群中,LR提供了更好的预后。更大的切缘长度和更高的切缘肿瘤比(MTR)与STAS+患者的OS和RFS的改善独立相关,但与接受SR的STAS -患者无关。在接受SR的STAS+患者中,切点分析确定了切缘长度的阈值为2.5 cm, MTR的阈值为1.7 cm,这在外部多中心队列中得到了验证。这些截止值对于病理性内脏性胸膜侵犯、淋巴血管侵犯或淋巴结受累的患者以及接受节段切除术或楔形切除术的患者仍然有效。结论在周围型cIA1-2 NSCLC中,STAS状态可改变切除范围和切缘对预后的影响。对于STAS+患者,推荐SR切缘长度≥2.5 cm或MTR≥1.7,以获得与LR相当的肿瘤学结果。
{"title":"Threshold of adequate resection margin for sub-lobar resection in peripheral clinical stage IA1-2 non-small cell lung cancer with tumor spread through air spaces","authors":"Hanbo Pan ,&nbsp;Hui Yin ,&nbsp;Wanyu Li ,&nbsp;Weicheng Kong ,&nbsp;Jiaqi Zhang ,&nbsp;Hang Chen ,&nbsp;Zhen Ge ,&nbsp;Yu Tian ,&nbsp;Junwei Ning ,&nbsp;Zhizhuo Dai ,&nbsp;Weiyang Huang ,&nbsp;Liang Fang ,&nbsp;Min Zheng ,&nbsp;Guomo Ruan ,&nbsp;Zhongjie Chen ,&nbsp;Ming Zhang ,&nbsp;Xiaomin Niu ,&nbsp;Jia Huang ,&nbsp;Chengwei Zhou ,&nbsp;Guodong Xu ,&nbsp;Qingquan Luo","doi":"10.1016/j.lungcan.2025.108838","DOIUrl":"10.1016/j.lungcan.2025.108838","url":null,"abstract":"<div><h3>Objectives</h3><div>Sub-lobar resection (SR) is an established treatment for peripheral clinical stage IA1-2 (cIA1-2) non-small cell lung cancer (NSCLC). However, it may fail to achieve complete resection and is associated with worse survival than lobar resection (LR) in spread through air spaces (STAS)<sup>+</sup> populations. This study aims to define the threshold of an adequate SR margin that may yield survival outcomes comparable to LR in peripheral cIA1-2 STAS<sup>+</sup> NSCLC.</div></div><div><h3>Methods</h3><div>Consecutive patients with peripheral cIA1-2 (consolidation-to-tumor ratio &gt; 0.5) NSCLC who underwent surgery between 2010 and 2020 across seven high-volume institutions were retrospectively reviewed. Stabilized inverse probability of treatment weighting (IPTW) was applied to mitigate selection bias. The primary endpoint was overall survival (OS), and the secondary endpoint was recurrence-free survival (RFS).</div></div><div><h3>Results</h3><div>A total of 6,027 STAS<sup>+</sup> and 15,994 STAS<sup>−</sup> patients were included. IPTW analyses demonstrated that SR was associated with improved long-term outcomes in STAS<sup>−</sup> populations, whereas LR provided superior outcomes in STAS<sup>+</sup> populations. Greater resection margin length and higher margin-to-tumor ratio (MTR) were independently associated with improved OS and RFS in STAS<sup>+</sup> but not in STAS<sup>−</sup> patients undergoing SR. Among STAS<sup>+</sup> patients undergoing SR, cut-point analysis identified threshold values of 2.5 cm for resection margin length and 1.7 for MTR, which were validated in an external multi-center cohort. These cutoff values remained effective in patients with pathological visceral pleural invasion, lymphovascular invasion, or nodal involvement, and in those undergoing either segmentectomy or wedge resection.</div></div><div><h3>Conclusions</h3><div>In peripheral cIA1-2 NSCLC, STAS status may modify the prognostic impact of both resection extent and margin. For STAS<sup>+</sup> patients, an SR margin length of ≥2.5 cm or an MTR of ≥1.7 may be recommended to achieve oncologic outcomes comparable to LR.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"210 ","pages":"Article 108838"},"PeriodicalIF":4.4,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145518053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Letter to the Editor: On the clinical irrelevance of SUCRA rankings in relapsed small-cell lung cancer 致编辑的信:关于SUCRA排名在复发小细胞肺癌中的临床无关性
IF 4.4 2区 医学 Q1 ONCOLOGY Pub Date : 2025-11-12 DOI: 10.1016/j.lungcan.2025.108837
Arif Hakan Önder
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引用次数: 0
NHWD-870 suppresses tumor proliferation via the BRD4/STRADA/CCND1 axis in small cell lung cancer NHWD-870在小细胞肺癌中通过BRD4/STRADA/CCND1轴抑制肿瘤增殖
IF 4.4 2区 医学 Q1 ONCOLOGY Pub Date : 2025-11-12 DOI: 10.1016/j.lungcan.2025.108841
Linrui Ma , Xiangyu Zhang , Shidong Xu , Jiacheng Dai , Zhe Huang , Zhaohui Ruan , Yuda Zhang , Xuexue Zhou , Yuanze Sun , Yahui Chen , Huan Yan , Chun Zou , Si Qi Xiang , Jingyi Li , Yangqian Chen , Tian Xu , Renzhi Zhang , Dan Yang , Fang Tian , Nachuan Zou , Yongchang Zhang

Background

Small cell lung cancer (SCLC) is a highly aggressive malignancy with poor prognosis and limited therapeutic options. The lack of effective targeted therapies for SCLC is a major limitation of this field. Bromodomain and Extra-Terminal (BET) inhibitors have emerged as a promising class of anticancer agents. This study aimed to evaluate the preclinical efficacy and mechanism of action of NHWD-870, a novel BET inhibitor targeting BRD4, in SCLC.

Method

The therapeutic effects of NHWD-870 on SCLC have been validated through compassionate use. The anti-tumor effects of NHWD-870 were explored using in vitro and in vivo models. CCK-8 assays and flow cytometry were utilized to examine cell viability, apoptosis, and mechanisms of cell cycle arrest. The in vivo effectiveness of NHWD-870 was evaluated using cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models of SCLC. Mechanistic studies involving RNA sequencing, Western blotting, qPCR, and transfection were conducted to investigate and confirm the underlying mechanisms of NHWD-870.

Result

Our study observed the efficacy of NHWD-870 in a patient with SCLC. NHWD-870 demonstrated robust anti-tumor activity against SCLC in both in vitro and in vivo models, effectively halting tumor growth, inducing apoptosis, and disrupting the cell cycle. RNA sequencing confirmed that the cell cycle is its primary pathway of action, with BRD4, STRADA, and CCND1 identified as key targets.

Conclusion

NHWD-870 exhibits anti-tumor activity both in vitro and in vivo against SCLC, primarily by regulating the BRD4/STRADA/CCND1 axis and inhibiting the transition of the cell cycle from the G1 phase to the S phase. These findings highlight the therapeutic potential of NHWD-870 as a novel BET inhibitor for SCLC treatment and provide a molecular basis for further clinical development.
背景:小细胞肺癌(SCLC)是一种高度侵袭性的恶性肿瘤,预后差,治疗选择有限。缺乏针对SCLC的有效靶向治疗是该领域的主要限制。溴域和外端(BET)抑制剂已成为一类很有前途的抗癌药物。本研究旨在评估新型靶向BRD4的BET抑制剂NHWD-870在SCLC中的临床前疗效和作用机制。方法通过体恤应用验证NHWD-870对SCLC的治疗效果。通过体外和体内模型探讨NHWD-870的抗肿瘤作用。CCK-8检测和流式细胞术检测细胞活力、凋亡和细胞周期阻滞机制。采用SCLC细胞系来源的异种移植(CDX)和患者来源的异种移植(PDX)模型评估NHWD-870的体内有效性。机制研究包括RNA测序、Western blotting、qPCR和转染,以调查和确认NHWD-870的潜在机制。结果一项研究观察了NHWD-870治疗1例SCLC的疗效。NHWD-870在体外和体内模型中都显示出强大的抗SCLC活性,有效地阻止肿瘤生长,诱导细胞凋亡,破坏细胞周期。RNA测序证实细胞周期是其主要作用途径,BRD4、STRADA和CCND1被确定为关键靶点。结论nhwd -870主要通过调控BRD4/STRADA/CCND1轴,抑制细胞周期从G1期向S期的转变,在体外和体内均表现出抗SCLC的活性。这些发现突出了NHWD-870作为SCLC治疗的新型BET抑制剂的治疗潜力,并为进一步的临床开发提供了分子基础。
{"title":"NHWD-870 suppresses tumor proliferation via the BRD4/STRADA/CCND1 axis in small cell lung cancer","authors":"Linrui Ma ,&nbsp;Xiangyu Zhang ,&nbsp;Shidong Xu ,&nbsp;Jiacheng Dai ,&nbsp;Zhe Huang ,&nbsp;Zhaohui Ruan ,&nbsp;Yuda Zhang ,&nbsp;Xuexue Zhou ,&nbsp;Yuanze Sun ,&nbsp;Yahui Chen ,&nbsp;Huan Yan ,&nbsp;Chun Zou ,&nbsp;Si Qi Xiang ,&nbsp;Jingyi Li ,&nbsp;Yangqian Chen ,&nbsp;Tian Xu ,&nbsp;Renzhi Zhang ,&nbsp;Dan Yang ,&nbsp;Fang Tian ,&nbsp;Nachuan Zou ,&nbsp;Yongchang Zhang","doi":"10.1016/j.lungcan.2025.108841","DOIUrl":"10.1016/j.lungcan.2025.108841","url":null,"abstract":"<div><h3>Background</h3><div>Small cell lung cancer (SCLC) is a highly aggressive malignancy with poor prognosis and limited therapeutic options. The lack of effective targeted therapies for SCLC is a major limitation of this field. Bromodomain and Extra-Terminal (BET) inhibitors have emerged as a promising class of anticancer agents. This study aimed to evaluate the preclinical efficacy and mechanism of action of NHWD-870, a novel BET inhibitor targeting BRD4, in SCLC.</div></div><div><h3>Method</h3><div>The therapeutic effects of NHWD-870 on SCLC have been validated through compassionate use. The anti-tumor effects of NHWD-870 were explored using in vitro and in vivo models. CCK-8 assays and flow cytometry were utilized to examine cell viability, apoptosis, and mechanisms of cell cycle arrest. The in vivo effectiveness of NHWD-870 was evaluated using cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models of SCLC. Mechanistic studies involving RNA sequencing, Western blotting, qPCR, and transfection were conducted to investigate and confirm the underlying mechanisms of NHWD-870.</div></div><div><h3>Result</h3><div>Our study observed the efficacy of NHWD-870 in a patient with SCLC. NHWD-870 demonstrated robust anti-tumor activity against SCLC in both in vitro and in vivo models, effectively halting tumor growth, inducing apoptosis, and disrupting the cell cycle. RNA sequencing confirmed that the cell cycle is its primary pathway of action, with BRD4, STRADA, and CCND1 identified as key targets.</div></div><div><h3>Conclusion</h3><div>NHWD-870 exhibits anti-tumor activity both in vitro and in vivo against SCLC, primarily by regulating the BRD4/STRADA/CCND1 axis and inhibiting the transition of the cell cycle from the G1 phase to the S phase. These findings highlight the therapeutic potential of NHWD-870 as a novel BET inhibitor for SCLC treatment and provide a molecular basis for further clinical development.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"210 ","pages":"Article 108841"},"PeriodicalIF":4.4,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145518092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Higher lung cancer risk among female never-smokers than males in a large married couple study 一项大型已婚夫妇研究显示,从不吸烟的女性患肺癌的风险高于男性
IF 4.4 2区 医学 Q1 ONCOLOGY Pub Date : 2025-11-08 DOI: 10.1016/j.lungcan.2025.108836
Hui Cai , Xiao-Ou Shu , Shenghui Wu , Yu-Tang Gao , Qing Lan , Nathaniel Rothman , Wei Zheng , Gong Yang

Background

Whether female being more susceptible to lung cancer among never smokers (LCNS) than males has been a long-standing debate.

Method

A total of 26,339 married heterosexual couples included in this cohort study. Truncated (40–89) age-standardized incidence rates and incidence rate ratio (IRR) of lung cancer were calculated and compared between the two sexes. Cox regression models were used to estimate hazard ratio (HR) for evaluating sex differences in lung cancer risk.

Results

In this large couples cohort study the prevalence of ever smoking was 2.1 % in wives and 65.4 % in husbands. Over a median follow-up of 12.5 years, incident lung cancer was documented in 293 wives and 500 husbands. The truncated age-standardized incidence rate per 100,000 person-years in all couples was significantly lower in wives (56.1) than their husbands (117.4), with an IRR of 0.48 for wives vs husbands. A similar pattern was observed among dual-smoker couples. However, the sex difference diminished when further adjusting for the duration and intensity of cigarette smoking. In contrast, among dual-nonsmoker couples, the corresponding age-standardized rate was significantly higher in wives (52.6) than their husbands (33.4), with an IRR of 1.57. Multivariable adjustment did not alter the result, with an HR for wives vs husbands of 1.54 (95 % CI, 1.05–2.27).

Conclusions

This study, for the first time, using a large cohort of married couples, demonstrates that females are more susceptible to LCNS than males.
背景:从不吸烟者(LCNS)中女性是否比男性更容易患肺癌一直是一个长期争论的问题。方法:本队列研究共纳入26339对已婚异性恋夫妇。计算截断的(40-89)年龄标准化肺癌发病率和发病率比(IRR),并比较两性之间的差异。采用Cox回归模型估计肺癌风险比(HR),以评估肺癌风险的性别差异。结果在这项大型夫妻队列研究中,妻子和丈夫的吸烟率分别为2.1%和65.4%。在中位12.5年的随访中,293名妻子和500名丈夫罹患肺癌。在所有夫妇中,每10万人年的截短年龄标准化发病率,妻子(56.1)明显低于丈夫(117.4),妻子与丈夫的IRR为0.48。在双吸烟者中也观察到类似的模式。然而,当进一步调整吸烟的持续时间和强度时,性别差异就减小了。相比之下,在双不吸烟夫妇中,相应的年龄标准化率,妻子(52.6)明显高于丈夫(33.4),IRR为1.57。多变量调整没有改变结果,妻子对丈夫的HR为1.54 (95% CI, 1.05-2.27)。结论:这项研究首次使用了大量的已婚夫妇,表明女性比男性更容易患LCNS。
{"title":"Higher lung cancer risk among female never-smokers than males in a large married couple study","authors":"Hui Cai ,&nbsp;Xiao-Ou Shu ,&nbsp;Shenghui Wu ,&nbsp;Yu-Tang Gao ,&nbsp;Qing Lan ,&nbsp;Nathaniel Rothman ,&nbsp;Wei Zheng ,&nbsp;Gong Yang","doi":"10.1016/j.lungcan.2025.108836","DOIUrl":"10.1016/j.lungcan.2025.108836","url":null,"abstract":"<div><h3>Background</h3><div>Whether female being more susceptible to lung cancer among never smokers (LCNS) than males has been a long-standing debate.</div></div><div><h3>Method</h3><div>A total of 26,339 married heterosexual couples included in this cohort study. Truncated (40–89) age-standardized incidence rates and incidence rate ratio (IRR) of lung cancer were calculated and compared between the two sexes. Cox regression models were used to estimate hazard ratio (HR) for evaluating sex differences in lung cancer risk.</div></div><div><h3>Results</h3><div>In this large couples cohort study the prevalence of ever smoking was 2.1 % in wives and 65.4 % in husbands. Over a median follow-up of 12.5 years, incident lung cancer was documented in 293 wives and 500 husbands. The truncated age-standardized incidence rate per 100,000 person-years in all couples was significantly lower in wives (56.1) than their husbands (117.4), with an IRR of 0.48 for wives vs husbands. A similar pattern was observed among dual-smoker couples. However, the sex difference diminished when further adjusting for the duration and intensity of cigarette smoking. In contrast, among dual-nonsmoker couples, the corresponding age-standardized rate was significantly higher in wives (52.6) than their husbands (33.4), with an IRR of 1.57. Multivariable adjustment did not alter the result, with an HR for wives vs husbands of 1.54 (95 % CI, 1.05–2.27).</div></div><div><h3>Conclusions</h3><div>This study, for the first time, using a large cohort of married couples, demonstrates that females are more susceptible to LCNS than males.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"210 ","pages":"Article 108836"},"PeriodicalIF":4.4,"publicationDate":"2025-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145518089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Tumor heterogeneity involving SCLC with a single exon deletion in RB1 and adenocarcinoma with EGFR-L718V mutation in EGFR-TKI–resistant lung cancer 肿瘤异质性涉及RB1单外显子缺失的SCLC和egfr - tki耐药肺癌中EGFR-L718V突变的腺癌。
IF 4.4 2区 医学 Q1 ONCOLOGY Pub Date : 2025-11-08 DOI: 10.1016/j.lungcan.2025.108833
Sho Kakuto , Ken Uchibori , Yuri Yamamoto , Eisaku Miyauchi , Makoto Nishio , Hisatoshi Sugiura , Ryohei Katayama

Introduction

EGFR tyrosine kinase inhibitors (EGFR-TKIs) have significantly improved the outcomes of EGFR-mutant non-small cell lung cancer (NSCLC); however, resistance commonly develops. While secondary EGFR mutations (e.g., C797S) and histological transformations are known mechanisms, their coexistence at distinct sites is rarely documented.

Methods

We established patient-derived cell lines from pleural effusion and mediastinal lymph node metastasis before and after osimertinib resistance in a patient with EGFR L858R–mutated NSCLC. Resistance mechanisms were characterized using cell viability assays, Western blotting, Sanger sequencing, RNA sequencing, and whole-exome sequencing.

Results

Pleural effusion–derived cells (JFCR-330-4 and -7) retained adenocarcinoma morphology and harbored an acquired EGFR L718V mutation, causing resistance to first-, third- and next-generation TKIs but sensitivity to second-generation TKI afatinib. Conversely, mediastinal lymph node–derived cells (JFCR-330-5) exhibited small cell lung cancer (SCLC)-like morphology, low EGFR expression, high neuroendocrine marker expression, and maintained EGFR L858R. RNA sequencing revealed SCLC-associated transcriptional signatures, while whole-exome and Sanger sequencing identified a small deletion in RB1 gene around exon 19 and a concurrent TP53 mutation, collectively suggesting transformation into SCLC.

Conclusion

Spatially distinct and simultaneous resistance mechanisms, namely, EGFR L718V mutation and SCLC transformation, contributed to osimertinib resistance. The detection of RB1 2.4 kb small deletion in RB1 gene highlights the importance of deep genomic profiling. Multi-site biopsy and molecular diagnostics are necessary to guide treatment decisions in EGFR-TKI–resistant NSCLC.
简介:EGFR酪氨酸激酶抑制剂(EGFR- tkis)显著改善了EGFR突变型非小细胞肺癌(NSCLC)的预后;然而,通常会产生耐药性。虽然继发性EGFR突变(如C797S)和组织学转化是已知的机制,但它们在不同位点的共存却很少有文献记载。方法:我们建立了一名EGFR l858r突变的非小细胞肺癌患者在奥西替尼耐药前后的胸膜积液和纵隔淋巴结转移患者来源的细胞系。利用细胞活力测定、Western blotting、Sanger测序、RNA测序和全外显子组测序来表征耐药机制。结果:胸腔积液源性细胞(JFCR-330-4和-7)保留了腺癌形态,并携带获得性EGFR L718V突变,导致对第一代、第三代和下一代TKI耐药,但对第二代TKI阿法替尼敏感。相反,纵隔淋巴结源性细胞(JFCR-330-5)表现出小细胞肺癌(SCLC)样形态,EGFR表达低,神经内分泌标志物表达高,EGFR L858R维持不变。RNA测序揭示了SCLC相关的转录特征,而全外显子组和Sanger测序发现外显子19周围RB1基因的小缺失和并发的TP53突变,共同提示转化为SCLC。结论:EGFR L718V突变和SCLC转化在空间上不同且同时发生的耐药机制促成了奥西替尼的耐药。RB1基因中RB1 2.4 kb小缺失的检测凸显了深度基因组图谱的重要性。多部位活检和分子诊断对于指导egfr - tki耐药NSCLC的治疗决策是必要的。
{"title":"Tumor heterogeneity involving SCLC with a single exon deletion in RB1 and adenocarcinoma with EGFR-L718V mutation in EGFR-TKI–resistant lung cancer","authors":"Sho Kakuto ,&nbsp;Ken Uchibori ,&nbsp;Yuri Yamamoto ,&nbsp;Eisaku Miyauchi ,&nbsp;Makoto Nishio ,&nbsp;Hisatoshi Sugiura ,&nbsp;Ryohei Katayama","doi":"10.1016/j.lungcan.2025.108833","DOIUrl":"10.1016/j.lungcan.2025.108833","url":null,"abstract":"<div><h3>Introduction</h3><div>EGFR tyrosine kinase inhibitors (EGFR-TKIs) have significantly improved the outcomes of EGFR-mutant non-small cell lung cancer (NSCLC); however, resistance commonly develops. While secondary EGFR mutations (e.g., C797S) and histological transformations are known mechanisms, their coexistence at distinct sites is rarely documented.</div></div><div><h3>Methods</h3><div>We established patient-derived cell lines from pleural effusion and mediastinal lymph node metastasis before and after osimertinib resistance in a patient with EGFR L858R–mutated NSCLC. Resistance mechanisms were characterized using cell viability assays, Western blotting, Sanger sequencing, RNA sequencing, and whole-exome sequencing.</div></div><div><h3>Results</h3><div>Pleural effusion–derived cells (JFCR-330-4 and -7) retained adenocarcinoma morphology and harbored an acquired EGFR L718V mutation, causing resistance to first-, third- and next-generation TKIs but sensitivity to second-generation TKI afatinib. Conversely, mediastinal lymph node–derived cells (JFCR-330-5) exhibited small cell lung cancer (SCLC)-like morphology, low EGFR expression, high neuroendocrine marker expression, and maintained EGFR L858R. RNA sequencing revealed SCLC-associated transcriptional signatures, while whole-exome and Sanger sequencing identified a small deletion in <em>RB1</em> gene around exon 19 and a concurrent <em>TP53</em> mutation, collectively suggesting transformation into SCLC.</div></div><div><h3>Conclusion</h3><div>Spatially distinct and simultaneous resistance mechanisms, namely, EGFR L718V mutation and SCLC transformation, contributed to osimertinib resistance. The detection of RB1 2.4 kb small deletion in <em>RB1</em> gene highlights the importance of deep genomic profiling. Multi-site biopsy and molecular diagnostics are necessary to guide treatment decisions in EGFR-TKI–resistant NSCLC.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"210 ","pages":"Article 108833"},"PeriodicalIF":4.4,"publicationDate":"2025-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145564309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Impact of immune-related and non-immune related hospital admissions on survival of patients with non-small cell lung cancer receiving first-line immunotherapy 免疫相关和非免疫相关住院对接受一线免疫治疗的非小细胞肺癌患者生存的影响
IF 4.4 2区 医学 Q1 ONCOLOGY Pub Date : 2025-11-07 DOI: 10.1016/j.lungcan.2025.108832
Adam Khorasanchi , Mingjia Li , Songzhu Zhao , Lai Wei , Evelyn Goodyear , Kevin Ho , Hamzah Abu-Sbeih , Austin Secor , Erin M. Bertino , Peter G. Shields , Logan Roof , Jinesh Gheeya , Kai He , Jacob Kaufman , Regan Memmott , Asrar Alahmadi , David P. Carbone , Gregory A. Otterson , Alexa Meara , Carolyn J. Presley , Dwight H. Owen

Background

Patients with metastatic non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs) are at risk for severe immune-related adverse events (irAEs). Limited data exists on the association between severe irAEs requiring hospitalization (irAEh) and overall survival (OS) in patients with NSCLC who received front-line ICIs, as well as risk factors for irAEh.

Methods

Electronic medical records of consecutive patients with metastatic NSCLC treated with front-line pembrolizumab with or without chemotherapy from 2017 to 2022 were assessed retrospectively. An irAEh was defined as any severe irAE requiring hospitalization within 1 year of ICI initiation. Clinical characteristics for the entire cohort were reported descriptively. Kaplan-Meier survival analysis and the Cox proportional hazard model were used to assess the OS and HR between groups.

Results

Among 312 patients, 203 (65 %) were hospitalized for any reason within 1 year of initiating pembrolizumab, including 37 (12 %) for irAEs. irAEh and overall hospitalization rates did not differ for patients treated with pembrolizumab alone compared to pembrolizumab in combination with chemotherapy. The most common reasons for irAEh were pneumonitis and colitis. Patients with irAEh experienced significantly shorter median OS (8.6 months; 95 % CI: 5.0–19.9) compared to those without irAEh (22.7 months; 95 % CI: 18.2–27.4; P = 0.027). Patients who experienced early-onset irAEh (<6 months) had a significantly shorter median OS of 5.4 months (95 % CI: 2.7–8.6) compared to those with late-onset irAEh (≥6 months), median OS not reached (NR); 95 % CI: 8.6-NR; P = 0.003. Patients hospitalized for any reason during the first year of treatment had a shorter median OS (11.2 months; 95 % CI: 9.5–15.2) than those who were not (49.4 months; 95 % CI: 39.5–62.4; P < 0.001).

Conclusions

Severe irAEs requiring hospitalization or hospitalization for any cause within the first year of initiating pembrolizumab among patients with NSCLC was associated with worse survival outcomes.
使用免疫检查点抑制剂(ICIs)治疗的转移性非小细胞肺癌(NSCLC)患者存在严重免疫相关不良事件(irAEs)的风险。在接受一线ICIs治疗的NSCLC患者中,需要住院治疗的严重irae (irAEh)与总生存率(OS)以及irAEh的危险因素之间的关联数据有限。方法回顾性评估2017年至2022年连续接受一线派姆单抗治疗或不接受化疗的转移性NSCLC患者的电子病历。irAE定义为ICI开始1年内需要住院治疗的任何严重irAE。描述性地报道了整个队列的临床特征。采用Kaplan-Meier生存分析和Cox比例风险模型评估组间OS和HR。结果312例患者中,203例(65%)患者在开始使用派姆单抗后1年内因任何原因住院,其中37例(12%)患者接受了irAEs治疗。与派姆单抗联合化疗相比,单独使用派姆单抗治疗的患者的irAEh和总体住院率没有差异。最常见的原因是肺炎和结肠炎。与没有irAEh的患者(22.7个月,95% CI: 18.2-27.4; P = 0.027)相比,irAEh患者的中位OS(8.6个月;95% CI: 5.0-19.9)显著缩短。与晚发irAEh(≥6个月)患者相比,早发irAEh患者的中位生存期显著缩短,为5.4个月(95% CI: 2.7-8.6),中位生存期未达到(NR);95% ci: 8.6-nr;p = 0.003。在治疗的第一年中,因任何原因住院的患者的中位OS(11.2个月;95% CI: 9.5-15.2)短于未住院的患者(49.4个月;95% CI: 39.5-62.4; P < 0.001)。在NSCLC患者中,在开始使用派姆单抗的第一年内,需要住院治疗或因任何原因住院的严重irae与较差的生存结果相关。
{"title":"Impact of immune-related and non-immune related hospital admissions on survival of patients with non-small cell lung cancer receiving first-line immunotherapy","authors":"Adam Khorasanchi ,&nbsp;Mingjia Li ,&nbsp;Songzhu Zhao ,&nbsp;Lai Wei ,&nbsp;Evelyn Goodyear ,&nbsp;Kevin Ho ,&nbsp;Hamzah Abu-Sbeih ,&nbsp;Austin Secor ,&nbsp;Erin M. Bertino ,&nbsp;Peter G. Shields ,&nbsp;Logan Roof ,&nbsp;Jinesh Gheeya ,&nbsp;Kai He ,&nbsp;Jacob Kaufman ,&nbsp;Regan Memmott ,&nbsp;Asrar Alahmadi ,&nbsp;David P. Carbone ,&nbsp;Gregory A. Otterson ,&nbsp;Alexa Meara ,&nbsp;Carolyn J. Presley ,&nbsp;Dwight H. Owen","doi":"10.1016/j.lungcan.2025.108832","DOIUrl":"10.1016/j.lungcan.2025.108832","url":null,"abstract":"<div><h3>Background</h3><div>Patients with metastatic non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs) are at risk for severe immune-related adverse events (irAEs). Limited data exists on the association between severe irAEs requiring hospitalization (irAEh) and overall survival (OS) in patients with NSCLC who received front-line ICIs, as well as risk factors for irAEh.</div></div><div><h3>Methods</h3><div>Electronic medical records of consecutive patients with metastatic NSCLC treated with front-line pembrolizumab with or without chemotherapy from 2017 to 2022 were assessed retrospectively. An irAEh was defined as any severe irAE requiring hospitalization within 1 year of ICI initiation. Clinical characteristics for the entire cohort were reported descriptively. Kaplan-Meier survival analysis and the Cox proportional hazard model were used to assess the OS and HR between groups.</div></div><div><h3>Results</h3><div>Among 312 patients, 203 (65 %) were hospitalized for any reason within 1 year of initiating pembrolizumab, including 37 (12 %) for irAEs. irAEh and overall hospitalization rates did not differ for patients treated with pembrolizumab alone compared to pembrolizumab in combination with chemotherapy. The most common reasons for irAEh were pneumonitis and colitis. Patients with irAEh experienced significantly shorter median OS (8.6 months; 95 % CI: 5.0–19.9) compared to those without irAEh (22.7 months; 95 % CI: 18.2–27.4; <em>P</em> = 0.027). Patients who experienced early-onset irAEh (&lt;6 months) had a significantly shorter median OS of 5.4 months (95 % CI: 2.7–8.6) compared to those with late-onset irAEh (≥6 months), median OS not reached (NR); 95 % CI: 8.6-NR; <em>P</em> = 0.003. Patients hospitalized for any reason during the first year of treatment had a shorter median OS (11.2 months; 95 % CI: 9.5–15.2) than those who were not (49.4 months; 95 % CI: 39.5–62.4; <em>P</em> &lt; 0.001).</div></div><div><h3>Conclusions</h3><div>Severe irAEs requiring hospitalization or hospitalization for any cause within the first year of initiating pembrolizumab among patients with NSCLC was associated with worse survival outcomes.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"210 ","pages":"Article 108832"},"PeriodicalIF":4.4,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145518052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Long-term survival comparison of first-line pembrolizumab versus pembrolizumab plus chemotherapy for patients with advanced non-small cell lung cancer: A multicenter propensity-matched cohort study 一线派姆单抗与派姆单抗联合化疗治疗晚期非小细胞肺癌患者的长期生存比较:一项多中心倾向匹配队列研究
IF 4.4 2区 医学 Q1 ONCOLOGY Pub Date : 2025-11-07 DOI: 10.1016/j.lungcan.2025.108835
Nao Shoshihara , Kinnosuke Matsumoto , Takayuki Shiroyama , Kiyohide Komuta , Akito Miyazaki , Motohiro Tamiya , Akihiro Tsukaguchi , Akihiro Tamiya , Tomoki Kuge , Yasuhiro Mihashi , Masahide Mori , Keijiro Yamauchi , Hidekazu Suzuki , Yuhei Kinehara , Hirotomo Machiyama , Satoshi Tanaka , Toshie Niki , Soichiro Kato , Yuki Nishikawa , Akio Osa , Atsushi Kumanogoh

Background

Pembrolizumab is currently used as a first-line therapy for EGFR- and ALK-negative advanced non-small cell lung cancer (NSCLC). However, whether pembrolizumab alone (P-mono) or combined with platinum chemotherapy (P-combo) provides superior long-term benefit remains unclear.

Methods

We retrospectively analyzed 392 patients with PD-L1 TPS ≥ 1 % treated first-line with P-mono (n = 194) or P-combo (n = 198) between 2019 and 2021. Propensity-score matching across 13 baseline variables yielded two well-balanced cohorts of 97 patients each, with a median follow-ups of 42.8 and 44.1 months, respectively.

Results

P-combo prolonged overall survival (OS) (median 31.8 vs 20.7 months; hazard ratio [HR] 0.67, 95 % confidence interval [CI] 0.46–0.96) and progression-free survival (12.5 vs 7.0 months; HR 0.59, 95 %CI 0.43–0.81). The 3- and 4-year OS rates were 49.8 % and 42.7 %, respectively, with P-combo, compared with 28.1 % and 22.3 % with P-mono. The 48-month restricted mean survival time also favored P-combo (p = 0.039). Additionally, greater benefits were observed among patients aged < 75 years, with ECOG performance status 0–1, PD-L1 TPS 1–49 %, and those using proton-pump inhibitors. Grade ≥ 3 treatment-related adverse events (TRAEs) were more frequent with P-combo (35 % vs 20 %, p = 0.024). However, treatment-related deaths (2 % each) and pneumonitis incidence and severity were comparable; cumulative toxicity curves plateaued after 3 years.

Conclusions

These findings suggest that P-combo showed a durable survival advantage over monotherapy and acceptable TRAEs in patients with PD-L1–positive NSCLC, identifying clinical subgroups most likely to benefit. Prospective randomized trials are warranted to validate these observations and guide optimal first-line treatment strategies.
背景:Pembrolizumab目前被用作EGFR和alk阴性晚期非小细胞肺癌(NSCLC)的一线治疗。然而,是否单独使用派姆单抗(P-mono)或联合铂化疗(P-combo)提供更好的长期获益仍不清楚。方法:我们回顾性分析了2019年至2021年间392例PD-L1 TPS≥1%的一线p -单药治疗患者(n = 194)或p -联合治疗患者(n = 198)。13个基线变量的倾向评分匹配产生了两组均衡的队列,每组97例患者,中位随访时间分别为42.8个月和44.1个月。结果:P-combo延长了总生存期(OS)(中位31.8 vs 20.7个月;风险比[HR] 0.67, 95%可信区间[CI] 0.46-0.96)和无进展生存期(12.5 vs 7.0个月;风险比0.59,95%可信区间[CI] 0.43-0.81)。P-combo组3年和4年生存率分别为49.8%和42.7%,而P-mono组分别为28.1%和22.3%。48个月的限制平均生存时间也有利于p组合(p = 0.039)。此外,在老年患者中观察到更大的获益。结论:这些发现表明,在pd - l1阳性非小细胞肺癌患者中,P-combo比单药治疗和可接受的trae具有持久的生存优势,确定了最有可能受益的临床亚组。有必要进行前瞻性随机试验来验证这些观察结果并指导最佳一线治疗策略。
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引用次数: 0
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Lung Cancer
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