IF 4.4 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2026-01-12 DOI: 10.1016/j.lungcan.2026.108917

Xiang Fei , Hao Wu , Mengxing Li , Jianmang Yu , Junyi Huang , Siqi Cao , Shiyou Wei , Qiuyun Wang , Wei Zhu , Zhize Yuan

Background

The protein Family with Sequence Similarity 83, Member A (FAM83A) is associated with the advancement of various tumors. This study examines the biological function and fundamental processes of FAM83A in lung squamous cell carcinoma (LUSC).

Methods

The GSE33479 dataset was used to compare FAM83A expression levels in LUSC, while the GSE73403 dataset explored its prognostic relevance. FAM83A was knocked down or over-expressed in LUSC cell lines, and CCK-8, colony formation, Transwell, and flow cytometry assays were performed to evaluate the effects of altered FAM83A expression on LUSC cell proliferation, apoptosis, invasion, and migration. Organoids and animal models were utilized to validate the impact of FAM83A knockdown on tumor growth. Finally, FAM83A-overexpressing LUSC cells were treated with SCH772984, a specific ERK inhibitor, to elucidate the potential mechanism underlying the oncogenic effect of FAM83A.

Results

FAM83A was upregulated in LUSC tissues and cell lines, with high expression correlating with shorter overall survival. Depletion of FAM83A reduced the migration, invasion, and proliferation of LUSC cells, accompanied by cell cycle arrest and increased apoptotic rate. Western blotting analyses showed that FAM83A knockdown upregulated E-cadherin, BAX, and Cleaved-PARP/Caspase 3, while downregulating N-cadherin, Vimentin, BCL2, and Cyclin D1. Conversely, overexpression of FAM83A in LUSC cells yielded the opposite phenotypes. In both organoid cultures and in vivo models, inhibition of FAM83A attenuated tumor growth. Rescue experiments demonstrated that SCH772984 reversed the malignant phenotypes induced by FAM83A over-expression, indicating that FAM83A promoted cell cycle progression, inhibits apoptosis, and enhances epithelial-mesenchymal transition (EMT) in LUSC through activating the ERK signaling pathway.

Conclusion

FAM83A is crucial in the advancement and spread of LUSC, as it promotes EMT and inhibits apoptosis via the activation of the ERK pathway. These findings highlight its potential as a strategic molecular target for the treatment of LUSC.

具有序列相似性83，成员A的蛋白家族（FAM83A）与多种肿瘤的进展有关。本研究探讨FAM83A在肺鳞状细胞癌（LUSC）中的生物学功能和基本过程。方法使用GSE33479数据集比较FAM83A在LUSC中的表达水平，而使用GSE73403数据集探讨其与预后的相关性。FAM83A在LUSC细胞系中被敲低或过表达，通过CCK-8、集落形成、Transwell和流式细胞术检测FAM83A表达改变对LUSC细胞增殖、凋亡、侵袭和迁移的影响。利用类器官和动物模型验证FAM83A敲低对肿瘤生长的影响。最后，用特异性ERK抑制剂SCH772984处理过表达FAM83A的LUSC细胞，以阐明FAM83A致癌作用的潜在机制。结果fam83a在LUSC组织和细胞系中表达上调，高表达与总生存期缩短相关。FAM83A的缺失减少了LUSC细胞的迁移、侵袭和增殖，并伴有细胞周期阻滞和凋亡率升高。Western blotting分析显示，FAM83A敲低可上调E-cadherin、BAX和Cleaved-PARP/Caspase 3，下调N-cadherin、Vimentin、BCL2和Cyclin D1。相反，FAM83A在LUSC细胞中的过表达产生相反的表型。在类器官培养和体内模型中，抑制FAM83A可减弱肿瘤生长。营救实验表明，SCH772984逆转了FAM83A过表达诱导的恶性表型，表明FAM83A通过激活ERK信号通路，促进LUSC细胞周期进程，抑制细胞凋亡，增强上皮-间质转化（EMT）。结论fam83a通过激活ERK通路促进EMT和抑制凋亡，在LUSC的进展和扩散中起着至关重要的作用。这些发现突出了它作为治疗LUSC的战略性分子靶点的潜力。

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引用次数: 0

KRAS-mutant advanced NSCLC: efficacy and clinical outcomes from network meta-analysis and real-world evidence kras突变晚期NSCLC：来自网络荟萃分析和真实世界证据的疗效和临床结果

IF 4.4 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2026-01-12 DOI: 10.1016/j.lungcan.2026.108930

Xiaoyu Gang , Yige Sun , Junli Hao , Suya Zhao , Yizheng Wang , Xinrui Yang , Heming Li , Mingfang Zhao

Background

KRAS is a common driver gene in non-small cell lung cancer (NSCLC). Owing to the absence of universally effective targeted agents and marked heterogeneity, optimal treatment selection for KRAS-mutant NSCLC remains uncertain. This study combined network meta-analysis (NMA) with real-world evidence to inform precision treatment strategies.

Methods

Thirteen randomized controlled trials were included in a Bayesian NMA to compare efficacy outcomes across regimens in KRAS-mutant and KRAS G12C-mutant NSCLC. In parallel, real-world data from advanced KRAS-mutant NSCLC patients treated at our center were analyzed.

Results

Across KRAS and G12C NMAs, immunotherapy-based regimens generally outperformed chemotherapy-based regimens. PD-(L)1 inhibitors monotherapy ranked highest for overall survival (OS), while chemotherapy plus PD-(L)1 inhibitors and anti-angiogenic therapy (anti-VEGF) ranked highest for progression-free survival (PFS). Chemotherapy plus dual immune checkpoint blockade (PD-(L)1 and CTLA-4) yielded a greater improvement in OS than in PFS. In our real-world cohort, first-line PD-(L)1 monotherapy achieved the best outcomes (objective response rate: 88.9%; median PFS: 22.2 months), followed by chemotherapy plus PD-(L)1 ± anti-VEGF. On multivariable analysis, ECOG performance status 0–1, PD-L1 TPS ≥ 50%, TMB ≥ 10 mut/Mb, and chemotherapy plus PD-(L)1 ± anti-VEGF were independently associated with longer first-line PFS. In subsequent lines, G12C inhibitors significantly improved outcomes versus other therapies, whereas non-G12C disease derived limited benefit from available strategies.

Conclusions

Immunotherapy constitutes the cornerstone of first-line therapy for KRAS-mutant NSCLC. Within this framework, PD-(L)1 monotherapy may be appropriate for carefully selected patients with high PD-L1 expression, whereas chemoimmunotherapy can extend benefit to broader subgroups; escalation with anti-VEGF or anti-CTLA-4 agents appears clinically promising and merits biomarker-driven prospective evaluation. KRAS G12C inhibitors are effective in later lines, while treatment options for non-G12C disease remain limited.

kras是非小细胞肺癌（NSCLC）中常见的驱动基因。由于缺乏普遍有效的靶向药物和明显的异质性，kras突变型NSCLC的最佳治疗选择仍然不确定。本研究将网络荟萃分析（NMA）与现实世界证据相结合，为精确治疗策略提供信息。方法在贝叶斯NMA中纳入13项随机对照试验，比较KRAS突变体和KRAS g12c突变体NSCLC不同方案的疗效结果。同时，我们分析了在本中心治疗的晚期kras突变NSCLC患者的真实数据。结果在KRAS和G12C nma中，基于免疫治疗的方案通常优于基于化疗的方案。PD-(L)1抑制剂单药治疗在总生存期（OS）中排名最高，而化疗加PD-(L)1抑制剂和抗血管生成治疗（抗vegf）在无进展生存期（PFS）中排名最高。化疗加双免疫检查点阻断（PD-(L)1和CTLA-4）对OS的改善比PFS更大。在我们的现实世界队列中，一线PD-(L)1单药治疗取得了最好的结果（客观缓解率：88.9%；中位PFS: 22.2个月），其次是化疗加PD-(L)1±抗vegf。在多变量分析中，ECOG表现状态0-1、PD- l1 TPS≥50%、TMB≥10 mut/Mb、化疗加PD-(L)1±抗vegf与较长的一线PFS独立相关。在随后的研究中，与其他疗法相比，G12C抑制剂显著改善了结果，而非G12C疾病从现有策略中获得的益处有限。结论免疫治疗是kras突变型非小细胞肺癌一线治疗的基石。在此框架下，PD-(L)1单药治疗可能适用于精心挑选的PD- l1高表达患者，而化学免疫治疗可以将益处扩展到更广泛的亚组；抗vegf或抗ctla -4药物的升级治疗在临床上很有前景，值得生物标志物驱动的前瞻性评估。KRAS G12C抑制剂在后期治疗中有效，而非G12C疾病的治疗选择仍然有限。

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引用次数: 0

Combined intrathecal therapy via Ommaya reservoir and whole-brain radiotherapy improves survival in EGFR-mutant NSCLC patients with leptomeningeal metastases: a real-world cohort study 一项真实世界队列研究：通过Ommaya储液池和全脑放疗联合鞘内治疗可提高egfr突变的脑膜轻转移NSCLC患者的生存率

IF 4.4 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2026-01-12 DOI: 10.1016/j.lungcan.2026.108918

Meifang Li , Haibo Wang , Wei Zhang , Dong Lin , Chongting Gao , Ying Chen , Cheng Lin , Zongyang Yu

Objective

This study aimed to evaluate the survival benefit of combined intrathecal treatment (IT) via Ommaya reservoir and whole-brain radiotherapy (WBRT) in EGFR-mutant non-small cell lung cancer (NSCLC) patients with leptomeningeal metastases (LM).

Methods

We retrospectively analyzed EGFR-mutant NSCLC patients with LM diagnosed between January 2019 and September 2024. Patients were included if they had cytologically or radiologically confirmed LM and prior EGFR-TKI exposure. Clinical data, cerebrospinal fluid (CSF) profiles (cytology, biochemistry, molecular features), and treatment details were collected. Local therapies included WBRT (30–37.5 Gy in 10–15 fractions) and IT pemetrexed via Ommaya reservoir (10–20 mg weekly for 4 weeks, then bi-weekly for 2 months, followed by monthly maintenance). Overall survival (OS) was analyzed using Kaplan-Meier method and Cox regression. A prognostic nomogram was developed and validated.

Results

Among 200 included patients, the median OS was 12.3 months (95% CI: 10.8–13.8). Patients receiving local therapy (n = 149) had longer OS than those without (n = 51) (13.1 vs. 8.8 months; HR = 0.78, p = 0.001). The combination of IT and WBRT was associated with the best survival outcome (median OS 18.5 months). In CSF analysis, the initial cytology positivity rate was 74.4% (128/172), and normal lactate dehydrogenase (LDH) and chloride levels were associated with longer OS (p < 0.05). Multivariate analysis identified ECOG score, prior third-generation TKI, third-generation TKI plus anti-angiogenic therapy, and local therapy as independent prognostic factors.

Conclusion

The combination of IT via Ommaya reservoir and WBRT may result in better survival in EGFR-mutant NSCLC patients with LM and represents a promising treatment strategy for this patient population.

目的本研究旨在评估经Ommaya储液池和全脑放疗（WBRT）联合鞘内治疗（IT）对egfr突变的非小细胞肺癌（NSCLC）轻脑膜转移（LM）患者的生存获益。方法回顾性分析2019年1月至2024年9月期间诊断为LM的egfr突变型NSCLC患者。如果患者有细胞学或放射学证实的LM和先前的EGFR-TKI暴露，则纳入患者。收集临床资料、脑脊液（CSF）资料（细胞学、生物化学、分子特征）和治疗细节。局部治疗包括WBRT （30-37.5 Gy， 10-15份）和IT培美曲塞通过Ommaya水库（每周10-20 mg，持续4周，然后每两周，持续2个月，然后每月维持）。采用Kaplan-Meier法和Cox回归分析总生存期（OS）。开发并验证了预后图。结果在纳入的200例患者中，中位OS为12.3个月（95% CI: 10.8-13.8）。接受局部治疗的患者（n = 149）比未接受局部治疗的患者（n = 51）有更长的OS （13.1 vs 8.8个月；HR = 0.78, p = 0.001）。IT和WBRT的结合与最佳生存结果（中位OS 18.5个月）相关。在CSF分析中，初始细胞学阳性率为74.4%(128/172)，正常乳酸脱氢酶（LDH）和氯化物水平与较长的生存期相关（p < 0.05）。多因素分析发现ECOG评分、既往第三代TKI、第三代TKI联合抗血管生成治疗和局部治疗是独立的预后因素。结论经Ommaya水库的IT和WBRT联合治疗egfr突变的非小细胞肺癌LM患者可能提高生存率，是一种很有前景的治疗策略。

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引用次数: 0

Corrigendum to "Global trends in lung cancer incidence and mortality by age, gender and morphology and forecast: A bootstrap-based analysis". [Lung Cancer 205 (2025) 108626]. “按年龄、性别和形态划分的肺癌发病率和死亡率的全球趋势和预测：基于自助的分析”的勘误表。[肺癌205(2025)108626]。

IF 4.4 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2026-01-11 DOI: 10.1016/j.lungcan.2026.108909

Jinto Edakkalathoor George, Preethi Sara George, Jagathnath K M Krishna, Aleyamma Mathew

引用次数: 0

Durvalumab-containing treatment for recurrent or metastatic pulmonary sarcomatoid carcinoma: A pooled post hoc analysis of two KCSG phase II trials 含durvalumab治疗复发或转移性肺肉瘤样癌：两项KCSG II期试验的合并事后分析

IF 4.4 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2026-01-11 DOI: 10.1016/j.lungcan.2026.108916

Dong Hyun Kim , Miso Kim , Jeonghwan Youk , Tae Min Kim , Gyeong-Won Lee , Se Hyun Kim , Yu Jung Kim , Jin-Soo Kim , Sook-Hee Hong , Mi Sun Ahn , Seong Hoon Shin , Dong-Wan Kim , Joo-Hang Kim , Bhumsuk Keam

Introduction

Pulmonary sarcomatoid carcinoma (PSC) is a rare cancer characterized by a high programmed death-ligand 1 (PD-L1) expression, suggesting a potential therapeutic benefit from immune checkpoint inhibitors. We investigated the efficacy of durvalumab-containing combination therapy and explored potential predictive biomarkers in patients with recurrent or metastatic (R/M) PSC.

Method

In this pooled post hoc analysis, data were integrated from two prospective phase II trials (NCT03022500 and NCT04224337) wherein durvalumab-containing combination therapies were evaluated in patients with R/M PSC. PD-L1 expression was assessed using 22C3 or SP263 assays, and circulating lymphocyte subsets were analyzed using flow cytometry.

Results

Overall, 33 patients were included, of whom 66.7 % had a PD-L1 tumor proportion score (TPS) ≥ 1 % and 45.5 % had a TPS ≥ 50 %. The overall response rate was 33.3 % (95 % confidence interval [CI], 18.0 %–51.8 %), and the disease control rate was 72.7 % (95 % CI, 54.5 %–86.7 %). The median progression-free survival and overall survival were 5.4 (95 % CI, 2.8–9.4) and 15.7 (95 % CI, 11.3–not estimated) months, respectively. PD-L1 expression was not associated with the response or survival outcomes. Patients who achieved disease control exhibited a higher proportion of circulating CD8⁺ T cells (mean, 28.5 % vs. 20.3 %, P = 0.083) and a lower CD4⁺/CD8⁺ ratio (median, 1.4 vs. 1.7, P = 0.048) than did those with progressive disease.

Conclusion

Durvalumab-containing combination therapy showed promising efficacy in patients with R/M PSC, irrespective of PD-L1 expression. A lower CD4⁺/CD8⁺ ratio may be associated with favorable disease control.

肺肉瘤样癌（PSC）是一种罕见的癌症，其特征是程序性死亡配体1 （PD-L1）高表达，提示免疫检查点抑制剂具有潜在的治疗益处。我们研究了含杜伐单抗联合治疗的疗效，并探索了复发或转移性（R/M） PSC患者的潜在预测生物标志物。方法在这项合并的事后分析中，整合了两项前瞻性II期试验（NCT03022500和NCT04224337）的数据，其中评估了durvalumab联合疗法对R/M PSC患者的治疗效果。用22C3或SP263检测PD-L1表达，用流式细胞术分析循环淋巴细胞亚群。结果共纳入33例患者，其中66.7%的患者PD-L1肿瘤比例评分(TPS)≥1%，45.5%的患者TPS≥50%。总有效率为33.3%(95%可信区间[CI]， 18.0% ~ 51.8%)，疾病控制率为72.7% （95% CI, 54.5% ~ 86.7%）。中位无进展生存期和总生存期分别为5.4个月（95% CI, 2.8-9.4）和15.7个月（95% CI， 11.3 -未估计）。PD-L1表达与反应或生存结果无关。获得疾病控制的患者比疾病进展的患者表现出更高的循环CD8+ T细胞比例（平均28.5%对20.3%,P = 0.083）和更低的CD4+/CD8+比值（中位数，1.4对1.7,P = 0.048）。结论杜伐单抗联合治疗对R/M型PSC患者具有良好的疗效，与PD-L1表达无关。较低的CD4+/CD8+比值可能与有利的疾病控制有关。

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引用次数: 0

SEZ6 expression and lineage plasticity in small cell lung cancer and transformed non-small cell lung cancer SEZ6在小细胞肺癌和转化非小细胞肺癌中的表达和谱系可塑性

IF 4.4 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2026-01-10 DOI: 10.1016/j.lungcan.2026.108913

Jennifer A. Marks , Kieran Sweeney , Andrew Elliott , Brinda Gupta , Ari VanderWalde , Sonam Puri , Misty Dawn Shields , Jorge J. Nieva , Heloisa P. Soares , Patrick C. Ma , Balazs Halmos , Stephen V. Liu

<div><h3>Introduction</h3><div>Small cell lung cancer (SCLC) and extrapulmonary neuroendocrine (NE) tumors are aggressive malignancies with limited treatment options. Seizure-related homolog 6 (SEZ6) is a potential therapeutic target, but its expression in these tumors remains poorly understood. Lineage plasticity contributes to resistance in non-small cell lung cancer (NSCLC), where some cases can undergo SCLC-transformation after targeted therapy. We aimed to characterize <em>SEZ6</em> expression across NE tumors and presumed NSCLC-to-SCLC transformations.</div></div><div><h3>Methods</h3><div>DNA and RNA sequencing were performed for SCLC, NSCLC, and NE samples. Samples were stratified by SEZ6 RNA expression quartiles and classified into subtypes based on ASCL1, NEUROD1, and POU2F3 expression. Significance was tested using the Mann-Whitney <em>U</em> test. Real-world overall survival was obtained from insurance claims data, with p-values calculated using the log-rank test. Paired samples for NSCLC-to-SCLC transformation were identified by sequential biopsies classified as NSCLC followed by SCLC.</div></div><div><h3>Results</h3><div>RNA sequencing was performed on 1318 SCLC and 2218 NE samples. Median SEZ6expression was higher in SCLC (39.7 transcripts per million (TPM)) than in NE tumors (20.8 TPM, p<0.0001) and NSCLC (1.34 TPM, p<0.001). Among NE tumors, median SEZ6 expression was highest in prostate (52.0 TPM, p=0.0016 vs SCLC) and lowest in adrenal gland tumors (1.2 TPM, p<0.0001 vs SCLC). In SCLC,SEZ6expression was positively correlated with ASCL1(p=0.44, p<0.0001) andNEUROD1(p=0.16, p<0.0001) expression but notPOU2F3(p=-0.04, p=0.1253). Median survival was longest in SEZ6-Q2 for both SCLC and NE (13.0 mos. and 33.7 mos., respectively). NSCLC-to-SCLC transformation samples showed numerically higher SEZ6 expression post-transformation (median: 86.2 vs 2.4 TPM).</div></div><div><h3>Conclusions</h3><div>SEZ6expression is higher in SCLC than in NE tumors, with notable heterogeneity by subtype, warranting consideration of expanded use of SEZ6-directed therapy.</div><div>Translational Relevance Statement:</div><div>This study establishes SEZ6 as a promising therapeutic target in small cell lung cancer (SCLC) and transformed non-small cell lung cancer (NSCLC), demonstrating its significantly elevated expression compared to neuroendocrine (NE) tumors and NSCLC. The positive correlation of <em>SEZ6</em> expression with NE lineage markers, particularly in <em>ASCL1</em> and <em>NEUROD1</em> subtypes, highlights its role as a lineage-specific marker, guiding the development of SEZ6-targeted antibody-drug conjugates (ADCs). Additionally, the increased <em>SEZ6</em> expression following NSCLC-to-SCLC transformation suggests that SEZ6-targeted therapies could address resistance mechanisms in transformed tumors. Importantly, the association be

小细胞肺癌（SCLC）和肺外神经内分泌（NE）肿瘤是侵袭性恶性肿瘤，治疗选择有限。癫痫相关同源物6 （SEZ6）是一个潜在的治疗靶点，但其在这些肿瘤中的表达仍然知之甚少。谱系可塑性有助于非小细胞肺癌（NSCLC）的耐药，其中一些病例在靶向治疗后可发生sclc转化。我们的目的是表征SEZ6在NE肿瘤中的表达，并推测nsclc到sclc的转化。方法对SCLC、NSCLC和NE样本进行dna和RNA测序。根据SEZ6 RNA表达四分位数对样品进行分层，并根据ASCL1、NEUROD1和POU2F3的表达情况将样品分为亚型。采用Mann-Whitney U检验进行显著性检验。真实世界的总生存率从保险索赔数据中获得，p值使用log-rank检验计算。配对样本的NSCLC到SCLC转化通过顺序活检分类为NSCLC和SCLC。结果对1318例SCLC和2218例NE样本进行了rna测序。SEZ6在SCLC中的中位表达（39.7转录本/百万（TPM））高于NE肿瘤（20.8 TPM, 0.0001）和NSCLC （1.34 TPM, p<0.001）。在NE肿瘤中，SEZ6中位表达在前列腺中最高（52.0 TPM, p=0.0016 vs SCLC），在肾上腺肿瘤中最低（1.2 TPM, p= 0.0001 vs SCLC）。在SCLC中，SEZ6表达与ASCL1 （p=0.44, p= 0.0001）和NEUROD1 （p=0.16, p= 0.0001）表达呈正相关，而与POU2F3表达无关（p=-0.04, p=0.1253）。SCLC和NE的SEZ6-Q2中位生存期最长（13.0个月）。33.7个。分别)。nsclc - sclc转化样本在转化后的SEZ6表达量更高（中位数：86.2 vs 2.4 TPM）。结论sez6在SCLC中的表达高于NE，且在亚型上存在显著的异质性，值得考虑扩大sez6定向治疗的应用。翻译相关性声明：本研究确立了SEZ6在小细胞肺癌（SCLC）和转化的非小细胞肺癌（NSCLC）中有前景的治疗靶点，与神经内分泌（NE）肿瘤和NSCLC相比，SEZ6的表达显著升高。SEZ6表达与NE谱系标记正相关，特别是在ASCL1和NEUROD1亚型中，突出了其作为谱系特异性标记的作用，指导了SEZ6靶向抗体-药物偶联物（adc）的发展。此外，在nsclc向sclc转化后SEZ6表达增加，表明SEZ6靶向治疗可以解决转化肿瘤的耐药机制。重要的是，高SEZ6表达与较短生存期之间的关联表明，将SEZ6状态整合到诊断工作流程中可以帮助根据风险对患者进行分层，并指导治疗决策。这项研究的结果将为未来的临床试验提供信息，旨在实施sez6靶向治疗，作为侵袭性NE恶性肿瘤精确肿瘤学策略的一部分。

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引用次数: 0

Nintedanib as switch maintenance treatment in malignant pleural mesothelioma (NEMO): A double-blind randomized phase II trial (EORTC-08112-LCG) 尼达尼布作为恶性胸膜间皮瘤（NEMO）的开关维持治疗：一项双盲随机II期试验（EORTC-08112-LCG）

IF 4.4 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2026-01-09 DOI: 10.1016/j.lungcan.2026.108906

Omar Abdel-Rahman , Paul Taylor , Mary O’Brien , Jo Raskin , Claudio Dazzi , Veerle Surmont , Sabrina Zonato , Robin Young , Anne-Claire Toffart , Petra Jankowska , Adam Hassani , Sandrine Marreaud , Luc Boone , Sanjay Popat

Introduction

Pleural mesothelioma (PM) is a lethal malignancy in which angiogenesis and progressive fibrosis drives disease. We evaluated angiogenesis inhibition using nintedanib monotherapy as switch maintenance in patients with PM that completed 4–6 cycles of prior platinum-pemetrexed chemotherapy. The trial was performed in parallel to the LUME-Meso trial in an era prior to routine immune checkpoint inhibitor use, when platinum-pemetrexed was standard of care.

Methods

This is a triple-blind, placebo-controlled, multicentric, randomized, phase II study. Patients with inoperable PM (all histologies) that completed 4–6 cycles of platinum-pemetrexed chemotherapy were randomized to nintedanib or placebo. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS) and safety.

Results

The trial was prematurely closed due to poor accrual after LUME-meso reported. 37 patients were randomized (18 to nintedanib, 19 to placebo). All analyses performed were descriptive. The median PFS was 3.4 months (95% CI: 2.83–5.82) and 4.6 months (95% CI: 3.65–13.17) for nintedanib and placebo arms, respectively (HR = 2.25, 95% CI: 1.07–4.73) with corresponding median OS of 13.1 months (95% CI: 10.22–26.02) and 38.9 months (95% CI: 18.66-NE) for nintedanib and placebo arms, respectively (HR = 2.38, 95% CI: 1.05–5.43). Two patients (11.1%) in the nintedanib arm experienced ≥ grade 3 treatment-related adverse events. Post progression treatment was balanced between arms but more patients in the placebo arm received immunotherapy (87% vs 54%).

Conclusions

Descriptive analyses suggest switch maintenance nintedanib does not improve PFS nor OS compared to placebo. Efficacy of the placebo arm may be related to imbalanced immunotherapy usage.

胸膜间皮瘤（PM）是一种由血管生成和进行性纤维化驱动的致死性恶性肿瘤。我们评估了尼达尼布单药治疗在完成4-6个周期铂-培美曲塞化疗的PM患者中的血管生成抑制作用。该试验与LUME-Meso试验同时进行，在常规免疫检查点抑制剂使用之前，铂-培美曲塞是标准治疗方案。方法：这是一项三盲、安慰剂对照、多中心、随机、II期研究。完成4-6个周期铂-培美曲塞化疗的不能手术的PM患者（所有组织学）被随机分配到尼达尼布或安慰剂组。主要终点为无进展生存期（PFS）。次要终点包括总生存期（OS）和安全性。结果LUME-meso报告后，由于累积不良，试验提前结束。37名患者被随机分配（18名接受尼达尼布治疗，19名接受安慰剂治疗）。所有的分析都是描述性的。尼达尼布组和安慰剂组的中位PFS分别为3.4个月（95% CI: 2.83-5.82）和4.6个月（95% CI: 3.65-13.17）（HR = 2.25, 95% CI: 1.07-4.73），相应的尼达尼布组和安慰剂组的中位OS分别为13.1个月（95% CI: 10.22-26.02）和38.9个月（95% CI: 18.66-NE）（HR = 2.38, 95% CI: 1.05-5.43）。尼达尼布组2例患者（11.1%）出现≥3级治疗相关不良事件。进展后治疗在两组之间是平衡的，但安慰剂组更多的患者接受了免疫治疗（87%对54%）。结论描述性分析表明，与安慰剂相比，切换维护尼达尼布不能改善PFS和OS。安慰剂组的疗效可能与不平衡的免疫治疗使用有关。

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引用次数: 0

Comparative efficacy and safety of post-TKI treatments for advanced EGFR-mutant non-small-cell lung cancer: a systematic review and network meta-analysis tki后治疗晚期egfr突变非小细胞肺癌的比较疗效和安全性：系统综述和网络荟萃分析

IF 4.4 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2026-01-08 DOI: 10.1016/j.lungcan.2026.108914

Yuanyuan Wang , Lin Zhang , Jianhua Zhan , Ling Wen , Xinyuan Zhao , Haishuang Sun , Xueyuan Chen , Yaxiong Zhang , Gang Chen , Yuanyuan Zhao , Yan Huang , Wenfeng Fang , Li Zhang , Dongchen Sun , Yunpeng Yang

Background

Despite the availability of several validated therapies, the optimal second-line regimen for EGFR-mutant non-small cell lung cancer (NSCLC) after tyrosine kinase inhibitor (TKI) failure remains uncertain.

Methods

The protocol was registered in PROSPERO (CRD420251157131). We systematically searched MEDLINE, Embase, CENTRAL, and conference proceedings (to Oct 20, 2025) for phase III randomized controlled trials (RCTs). A Bayesian network meta-analysis was performed. The primary outcome was progression-free survival (PFS). Secondary outcomes included overall survival (OS) and the incidence of grade ≥3 treatment-related adverse events (TRAEs).

Results

Eleven RCTs (3,650 patients, seven regimens) were included. Compared to chemotherapy, sacituzumab tirumotecan (SacTMT), amivantamab plus chemotherapy (Chemo-Ami), and chemo-immunotherapy plus anti-angiogenic agent (Chemo-IO-anti-VEGF) demonstrated superior PFS (HR 0.49, 0.48, 0.53, respectively) and OS (HR 0.60, 0.73, 0.83, respectively). SacTMT also significantly improved OS over chemo-immunotherapy (HR 0.68, 95 % CrI 0.48 to 0.95). Regarding safety, Chemo-Ami carried higher grade ≥3 TRAEs risk (OR 2.83, 95 % CrI 1.01 to 7.90) versus chemotherapy, while SacTMT and Chemo-IO-anti-VEGF demonstrated toxicity comparable to chemotherapy.

Conclusions

SacTMT, Chemo-Ami, and Chemo-IO-anti-VEGF offer superior efficacy over chemotherapy for EGFR-mutant NSCLC after TKI progression. SacTMT and Chemo-IO-anti-VEGF may have more favorable safety profiles than Chemo-Ami. This comparative evidence helps to inform clinical decision-making.

背景：尽管有几种有效的治疗方法，但酪氨酸激酶抑制剂（TKI）失效后egfr突变的非小细胞肺癌（NSCLC）的最佳二线治疗方案仍不确定。方法该方案在PROSPERO注册（CRD420251157131）。我们系统地检索了MEDLINE、Embase、CENTRAL和会议论文集（至2025年10月20日）的III期随机对照试验（rct）。采用贝叶斯网络进行meta分析。主要终点为无进展生存期（PFS）。次要结局包括总生存期（OS）和≥3级治疗相关不良事件（TRAEs）的发生率。结果纳入6项随机对照试验（共3650例患者，7个方案）。与化疗相比，舒妥珠单抗替鲁莫替康（SacTMT）、阿米万他单抗联合化疗（Chemo-Ami）和化疗免疫联合抗血管生成药物（Chemo-IO-anti-VEGF）的PFS （HR分别为0.49、0.48、0.53）和OS （HR分别为0.60、0.73、0.83）均优于化疗。与化疗免疫治疗相比，SacTMT也显著改善了OS （HR 0.68, 95% CrI 0.48 - 0.95）。在安全性方面，与化疗相比，Chemo-Ami具有更高的≥3级TRAEs风险（OR 2.83, 95% CrI 1.01至7.90），而SacTMT和Chemo-IO-anti-VEGF显示出与化疗相当的毒性。结论sactmt、Chemo-Ami和Chemo-IO-anti-VEGF治疗TKI进展后egfr突变型NSCLC的疗效优于化疗。SacTMT和Chemo-IO-anti-VEGF可能比Chemo-Ami具有更有利的安全性。这种比较证据有助于告知临床决策。

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引用次数: 0

Letter to the editor: treatment sequencing in synchronous oligometastatic NSCLC − the need for standardized patient selection Criteria 致编辑的信：同步少转移性NSCLC的治疗测序-需要标准化的患者选择标准

IF 4.4 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2026-01-07 DOI: 10.1016/j.lungcan.2026.108911

Peng Bai , Jun Zhang

引用次数: 0

Survival outcomes of patients with uncommon EGFR mutations in surgically resected lung adenocarcinoma: A multi-institutional real-world database study (CReGYT-01 EGFR study) 手术切除肺腺癌中罕见EGFR突变患者的生存结局：一项多机构真实世界数据库研究（CReGYT-01 EGFR研究）

IF 4.4 2区医学 Q1 ONCOLOGY

Lung Cancer

Pub Date : 2026-01-06 DOI: 10.1016/j.lungcan.2026.108908

Kazuki Hayasaka , Mototsugu Shimokawa , Naoki Haratake , Hirotsugu Notsuda , Shinya Katsumata , Akira Hamada , Kotaro Nomura , Kosuke Fujino , Mao Yoshikawa , Ken Suzawa , Kazuhiko Shien , Kenichi Suda , Shuta Ohara , Shota Fukuda , Ikuhiko Kinoshita , Shinkichi Takamori , Satoshi Muto , Yusuke Takanashi , Kiyomichi Mizuno , Takamitsu Hayakawa , Yoshinori Okada

Introduction

Uncommon epidermal growth factor receptor (EGFR) mutations (UCM) account for approximately 10% of EGFR-mutant lung adenocarcinoma (LUAD) cases; however, their prognostic impact remains unclear. This study aimed to evaluate postoperative outcomes in patients with UCM compared to those with common mutations (CM) using a large multicenter database.

Materials and methods

This retrospective study included 1,636 patients with EGFR-mutant LUAD who underwent complete resection between 2015 and 2018 at 21 Japanese institutions. Patients were classified into the CM and UCM groups. Recurrence-free survival (RFS), overall survival (OS), lung cancer-specific survival (LCSS), and survival after recurrence (SAR) were analyzed using univariable and multivariable analyses and the inverse probability of treatment weighting (IPTW) method.

Results

Among the patients, 1,441 (88.1%) had CM and 195 (11.9%) had UCM. RFS was comparable between the groups. However, patients with UCM showed significantly shorter OS and LCSS than those with CM (OS: multivariable hazard ratio [HR] 1.538, 95% confidence interval [CI] 1.003–2.359; LCSS: multivariable HR 1.803, 95% CI 1.064–3.056). This trend was consistently validated using IPTW methods. SAR was also significantly shorter in patients with UCM. Subtype-specific analyses revealed that patients with exon 20 insertions (Ex20ins) had a significantly worse prognosis than those with other UCMs.

Conclusion

Patients with UCM had significantly worse OS, LCSS, and SAR than those with CM despite similar RFS. These survival disadvantages in UCM were strongly associated with the Ex20ins subtype. These findings highlight the urgent need for novel perioperative treatments for patients with UCM, especially Ex20ins.

罕见的表皮生长因子受体（EGFR）突变（UCM）约占EGFR突变型肺腺癌（LUAD）病例的10%；然而，它们的预后影响仍不清楚。本研究旨在利用大型多中心数据库评估UCM患者与普通突变（CM）患者的术后预后。材料和方法本回顾性研究包括2015年至2018年在日本21家机构接受完全切除的1636例egfr突变LUAD患者。将患者分为CM组和UCM组。采用单变量和多变量分析及治疗加权逆概率（IPTW）法分析无复发生存期（RFS）、总生存期（OS）、肺癌特异性生存期（LCSS）和复发后生存期（SAR）。结果CM 1441例（88.1%），UCM 195例（11.9%）。两组间的RFS具有可比性。然而，UCM患者的OS和LCSS明显短于CM患者（OS：多变量风险比[HR] 1.538, 95%可信区间[CI] 1.003-2.359； LCSS：多变量风险比[HR] 1.803, 95%可信区间[CI] 1.064-3.056）。使用IPTW方法，这种趋势得到了一致的验证。UCM患者的SAR也明显较短。亚型特异性分析显示，外显子20插入（Ex20ins）的患者预后明显差于其他ucm患者。结论尽管RFS相似，但UCM患者的OS、LCSS和SAR均明显低于CM患者。UCM中的这些生存劣势与Ex20ins亚型密切相关。这些发现强调了UCM患者迫切需要新的围手术期治疗，特别是ex20in。

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引用次数: 0