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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 Pub Date : 2026-03-01 Epub 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
Amivantamab plus chemotherapy versus chemotherapy for first-line treatment of participants with EGFR exon 20 insertion-mutated advanced non-small cell lung cancer: PAPILLON Asia subgroup analysis 阿米万他单抗加化疗与化疗对EGFR外显子20插入突变晚期非小细胞肺癌患者的一线治疗:PAPILLON亚洲亚组分析
IF 4.4 2区 医学 Q1 ONCOLOGY Pub Date : 2026-03-01 Epub Date: 2026-02-02 DOI: 10.1016/j.lungcan.2026.109302
Caicun Zhou , Ke-Jing Tang , Baogang Liu , Sang-We Kim , Satoru Kitazono , Akira Ono , Muthukkumaran Thiagarajan , Jen-Yu Hung , Michael Boyer , Timuçin Çİl , Yu Yao , Rajnish Nagarkar , John Xie , Archan Bhattacharya , Honeylet Wortman-Vayn , Mahadi Baig , Trishala Agrawal , Patricia Lorenzini , Se-Hoon Lee , Byoung Chul Cho

Background

Amivantamab is a bispecific, epidermal growth factor receptor (EGFR) and MET-proto-oncogene (MET)-targeting antibody with immune cell-directing activity. In the global Phase 3 PAPILLON trial, amivantamab plus carboplatin-pemetrexed (amivantamab-chemotherapy) significantly improved progression-free survival (PFS) vs chemotherapy alone in previously untreated participants with locally advanced/metastatic NSCLC with EGFR exon 20 insertions (Ex20ins). We evaluated clinical outcomes in Asian participants in PAPILLON (NCT04538664).

Methods

Participants were randomized 1:1 to amivantamab-chemotherapy or chemotherapy alone. Study endpoints for this analysis were PFS by blinded independent central review (primary), objective response rate (ORR), duration of response (DoR), PFS after first subsequent therapy (PFS2), overall survival (OS), and safety (secondary). Crossover to amivantamab monotherapy was allowed when disease progressed on chemotherapy alone.

Results

Among 186 participants in the Asian sub-cohort, 97 received amivantamab-chemotherapy and 89 received chemotherapy. At median follow-up of 16.6 months, median PFS (95% confidence interval [CI]) in the amivantamab-chemotherapy/chemotherapy groups was 11.5/5.6 months (hazard ratio [HR] 0.34; 95%CI, 0.23–0.49; nominal p < 0.0001) arms. The ORR was 70% vs 51% (odds ratio 2.2, 95%CI, 1.2–3.9; nominal p = 0.012), DoR 10.1 vs 5.5 months. Median PFS2 was not estimable vs 18.8 months (HR 0.46, 95%CI 0.26–0.83; nominal p = 0.008), and median interim OS not estimable vs 24.4 months HR 0.65, 95%CI 0.34–1.24; nominal p = 0.189), respectively, despite substantial (73%) crossover. Safety profiles for both arms were similar to the overall PAPILLON population.

Conclusions

Amivantamab-chemotherapy demonstrated superior PFS vs chemotherapy and represents a new standard of care for first-line treatment of Asian participants with Ex20ins-mutated NSCLC.
背景:阿米万他抗是一种双特异性的表皮生长因子受体(EGFR)和MET原癌基因(MET)靶向抗体,具有免疫细胞定向活性。在全球3期PAPILLON试验中,amivantamab联合卡铂-培美曲塞(amivantamab-chemotherapy)显著改善了EGFR外显子20插入(Ex20ins)的局部晚期/转移性NSCLC患者的无进展生存期(PFS)。我们评估了PAPILLON (NCT04538664)在亚洲参与者中的临床结果。方法:参试者按1:1的比例随机分为阿米万他单化疗组和单独化疗组。该分析的研究终点为盲法独立中心评价的PFS(主要)、客观缓解率(ORR)、缓解持续时间(DoR)、首次后续治疗后的PFS (PFS2)、总生存期(OS)和安全性(次要)。当单独化疗的疾病进展时,允许交叉到阿米万他单药治疗。结果:在亚洲亚队列的186名参与者中,97名接受了阿米万他单化疗,89名接受了化疗。在中位随访16.6个月时,阿米万他抗化疗/化疗组的中位PFS(95%可信区间[CI])为11.5/5.6个月(风险比[HR] 0.34; 95%CI, 0.23-0.49; nominal p)结论:阿米万他抗化疗比化疗显示出更优的PFS,代表了ex20in突变的亚洲非小细胞肺癌患者一线治疗的新标准。
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引用次数: 0
Lung cancer in women: current evidence and future research priorities 女性肺癌:当前证据和未来研究重点。
IF 4.4 2区 医学 Q1 ONCOLOGY Pub Date : 2026-03-01 Epub Date: 2026-01-04 DOI: 10.1016/j.lungcan.2025.108905
Monireh Sadat Seyyedsalehi , Massimiliano Cani , Qian Wang , Chitra Thakur , Umberto Malapelle , Chung Yin Kong , Silvia Novello , Paolo Boffetta
Lung cancer (LC) remains the leading cause of cancer-related mortality among women worldwide. Compared to men, LC in women presents distinct epidemiologic, biological, and clinical characteristics. A large proportion of LC cases in women occur in never-smokers, underscoring the important roles of environmental exposures, genetic susceptibility, and hormonal influences in disease pathogenesis. LC in women also displays unique molecular profiles, with a higher prevalence of actionable alterations such as epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements, which inform targeted therapy selection. Despite advances in chemotherapy, targeted agents, and immunotherapy, sex-based differences in treatment efficacy, toxicity, and survivorship persist and remain incompletely understood. Additional barriers, including limited access to LC screening and the underrepresentation of women in clinical trials, further constrain the application of evidence-based interventions for women. This review synthesizes latest evidence on epidemiology, risk factors, molecular features, screening, treatment outcomes, and survivorship challenges in women with LC with a deep focus on novel approaches to overcome current barriers and disparities to improve prevention, early detection, treatment, and long-term survivorship care.
肺癌(LC)仍然是全球妇女癌症相关死亡的主要原因。与男性相比,女性LC表现出不同的流行病学、生物学和临床特征。很大一部分女性LC病例发生在从不吸烟的人群中,强调了环境暴露、遗传易感性和激素影响在疾病发病机制中的重要作用。女性LC也显示出独特的分子特征,具有更高的可操作改变发生率,如表皮生长因子受体(EGFR)突变和间变性淋巴瘤激酶(ALK)重排,这为靶向治疗选择提供了信息。尽管在化疗、靶向药物和免疫治疗方面取得了进展,但基于性别的治疗效果、毒性和生存率的差异仍然存在,并且仍然不完全清楚。其他障碍,包括获得LC筛查的机会有限和妇女在临床试验中的代表性不足,进一步限制了以证据为基础的妇女干预措施的应用。本综述综合了LC女性的流行病学、危险因素、分子特征、筛查、治疗结果和生存挑战的最新证据,并深入探讨了克服当前障碍和差距的新方法,以改善预防、早期发现、治疗和长期生存护理。
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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 Pub Date : 2026-03-01 Epub 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。
{"title":"KRAS-mutant advanced NSCLC: efficacy and clinical outcomes from network meta-analysis and real-world evidence","authors":"Xiaoyu Gang ,&nbsp;Yige Sun ,&nbsp;Junli Hao ,&nbsp;Suya Zhao ,&nbsp;Yizheng Wang ,&nbsp;Xinrui Yang ,&nbsp;Heming Li ,&nbsp;Mingfang Zhao","doi":"10.1016/j.lungcan.2026.108930","DOIUrl":"10.1016/j.lungcan.2026.108930","url":null,"abstract":"<div><h3>Background</h3><div><em>KRAS</em> 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 <em>KRAS</em>-mutant NSCLC remains uncertain. This study combined network meta-analysis (NMA) with real-world evidence to inform precision treatment strategies.</div></div><div><h3>Methods</h3><div>Thirteen randomized controlled trials were included in a Bayesian NMA to compare efficacy outcomes across regimens in <em>KRAS</em>-mutant and <em>KRAS</em> G12C-mutant NSCLC. In parallel, real-world data from advanced <em>KRAS</em>-mutant NSCLC patients treated at our center were analyzed.</div></div><div><h3>Results</h3><div>Across <em>KRAS</em> 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.</div></div><div><h3>Conclusions</h3><div>Immunotherapy constitutes the cornerstone of first-line therapy for <em>KRAS</em>-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.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"213 ","pages":"Article 108930"},"PeriodicalIF":4.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145981781","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
Diagnostic performance of monarch robotic bronchoscopy with and without mobile cone-beam CT support 君主机器人支气管镜在有和没有移动锥束CT支持下的诊断性能。
IF 4.4 2区 医学 Q1 ONCOLOGY Pub Date : 2026-03-01 Epub Date: 2026-01-10 DOI: 10.1016/j.lungcan.2026.108910
Jingjing Chen, Dakota McNierney, Joe G. Zein, Laszlo T. Vaszar, Karen L. Swanson, Natalya Azadeh, Kenneth K. Sakata

Background

Robotic-assisted bronchoscopy (RAB) is limited by CT-to-body divergence. Cone-beam CT (CBCT) may enhance tool-to-lesion alignment and diagnostic yield (DY), but the benefit of integrating mobile CBCT (mCBCT) into the MonarchTM RAB remains understudied. This is the first study to evaluate diagnostic performance between Monarch alone versus Monarch plus mCBCT for peripheral pulmonary lesion (PPL) biopsy, hypothesizing improved DY with the combined approach.

Methods

This single-center retrospective study examined adults undergoing RAB biopsy for PPLs (May 2019—March 2023), applying a strict DY definition. Clinical characteristics and outcomes were evaluated in Monarch and Monarch plus mCBCT groups.

Results

Of 331 cases, 179 used Monarch and 152 used Monarch plus mCBCT. There was no significant difference in baseline characteristics. DY was not different (70.9 % in Monarch vs 71.7 % in Monarch plus mCBCT, p = 0.976) nor were complication rates (7.3 % in Monarch vs. 3.9 % in Monarch plus mCBCT, p = 0.291). In the Monarch group, the procedure duration was longer (77 min in Monarch vs. 69 min in Monarch plus mCBCT, p = 0.002) and the radiation dose was lower (7.4 mGy in Monarch vs. 285.9 mGy in Monarch plus mCBCT, p < 0.001). Adjusted analysis demonstrated that mCBCT was not associated with improved DY (OR [95 % CI]: 1.33[0.78–2.28]) or reduced risk for complications (OR [95 % CI]: 0.41 [0.13; 1.14]). DY increased with larger nodule size but not with lesion location.

Conclusions

Evaluating outcomes across two sequential practice eras, the addition of mCBCT to Monarch RAB did not significantly improve DY or reduce complications but reduced procedure duration at the cost of increased radiation exposure.

Summary

- Evaluated diagnostic performance of Monarch™ vs. Monarch™ + mobile Cone-beam CT (mCBCT).
- Diagnostic yield and complication rates were similar.
- The mCBCT group had shorter procedure times and about 40-fold higher radiation doses.

Conference presentation

The study findings have been presented in American Association for Bronchology and Interventional Pulmonology Annual Conference in 2024.
The institutional review board approved all protocols (IRB 23–005284).
背景:机器人辅助支气管镜检查(RAB)受到ct -体发散的限制。锥形束CT (CBCT)可以提高工具到病变的对齐和诊断率(DY),但将移动CBCT (mCBCT)整合到MonarchTM RAB的好处仍有待研究。这是第一个评估君主单独与君主联合mCBCT对周围肺病变(PPL)活检诊断性能的研究,假设联合方法改善了DY。方法:本研究采用严格的DY定义,对2019年5月至2023年3月接受RAB活检的ppl成人进行了单中心回顾性研究。评估Monarch组和Monarch + mCBCT组的临床特征和结果。结果:331例患者中,君主179例,君主联合mCBCT 152例。两组的基线特征无显著差异。死亡率无差异(Monarch组70.9% vs Monarch + mCBCT组71.7%,p = 0.976),并发症发生率也无差异(Monarch组7.3% vs Monarch + mCBCT组3.9%,p = 0.291)。在Monarch组中,手术时间更长(Monarch组为77分钟,而Monarch + mCBCT组为69分钟,p = 0.002),辐射剂量更低(Monarch组为7.4 mGy,而Monarch组为285.9 mGy, p)。结论:评估两个连续实践时期的结果,在Monarch RAB中添加mCBCT并没有显著改善DY或减少并发症,但以增加辐射暴露为代价减少了手术时间。总结:-评估君主™与君主™+移动锥束CT (mCBCT)的诊断性能。诊断率和并发症发生率相似。- mCBCT组的手术时间更短,辐射剂量约高40倍。会议报告:该研究结果已在2024年美国支气管学和介入肺病学协会年会上发表。机构审查委员会批准了所有方案(IRB 23-005284)。
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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 Pub Date : 2026-03-01 Epub 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
Patient-reported outcomes and time to symptomatic progression from PAPILLON: amivantamab plus chemotherapy vs chemotherapy as first-line treatment of EGFR exon 20 insertion-mutated advanced NSCLC 患者报告的结果和从PAPILLON到症状进展的时间:阿米万他单抗加化疗vs化疗作为EGFR外显子20插入突变的晚期NSCLC的一线治疗
IF 4.4 2区 医学 Q1 ONCOLOGY Pub Date : 2026-03-01 Epub Date: 2025-10-03 DOI: 10.1016/j.lungcan.2025.108788
Luis Paz-Ares , Remi Veillon , Margarita Majem , Caicun Zhou , Ke-Jing Tang , Sang-We Kim , Gary Richardson , Nicolas Girard , Rachel E. Sanborn , Aaron S. Mansfield , Keunchil Park , Julia Schuchard , Joris Diels , Jan Sermon , Archan Bhattacharya , Patricia Lorenzini , Honeylet Wortman-Vayn , Roland E. Knoblauch , Trishala Agrawal , Mahadi Baig , Joshua K. Sabari

Background

Epidermal growth factor receptor (EGFR) exon 20 insertions (Ex20ins) are the third most common type of EGFR mutation, occurring in up to 12% of EGFR-mutated non-small cell lung cancers (NSCLC). Ex20ins-mutated NSCLC can be resistant to most approved tyrosine kinase inhibitors (TKIs). The Phase III PAPILLON trial (NCT04538664) demonstrated that amivantamab plus chemotherapy significantly improves progression-free survival (PFS) compared to chemotherapy alone, leading to its approval as a first-line treatment for patients with Ex20ins NSCLC. PAPILLON further evaluated patient-reported outcomes (PROs) and time to symptomatic progression (TTSP).

Methods

The open-label, multicenter trial randomized 308 treatment-naïve patients with advanced or metastatic NSCLC harboring Ex20ins to receive either amivantamab plus carboplatin-pemetrexed (n = 154) or chemotherapy alone (n = 154). TTSP was defined as the time to onset or worsening of lung cancer-related symptoms necessitating treatment change or clinical intervention, or death. PROs were assessed using the PROMIS PF8c and EORTC QLQ-C30.

Results

At 12 months, 77 % of patients in the amivantamab-chemotherapy arm remained free of symptomatic progression versus 60 % in the chemotherapy arm (HR, 0.67; 95 % CI, 0.46–0.98; p = 0.04). Physical functioning and global health status PROs were maintained in both arms, with a higher proportion of patients treated in the amivantamab-chemotherapy arm reporting stable or improved quality of life at 6 and 12 months.

Conclusions

Amivantamab plus chemotherapy significantly delays symptomatic progression without compromising health-related quality of life, reinforcing its role as a first-line treatment for Ex20ins-mutated NSCLC.
表皮生长因子受体(EGFR)外显子20插入(Ex20ins)是第三种最常见的EGFR突变类型,发生在高达12%的EGFR突变的非小细胞肺癌(NSCLC)中。ex20in突变的NSCLC可对大多数批准的酪氨酸激酶抑制剂(TKIs)产生耐药性。III期PAPILLON试验(NCT04538664)表明,与单独化疗相比,阿米万他单抗联合化疗可显著提高无进展生存期(PFS),从而使其被批准作为Ex20ins NSCLC患者的一线治疗药物。PAPILLON进一步评估了患者报告的结局(PROs)和症状进展时间(TTSP)。方法:该开放标签、多中心试验随机选取308例treatment-naïve携带Ex20ins的晚期或转移性NSCLC患者,接受阿米万他单抗联合卡铂-培美曲塞(n = 154)或单独化疗(n = 154)。TTSP定义为肺癌相关症状出现或恶化,需要改变治疗或临床干预,或死亡的时间。使用PROMIS PF8c和EORTC QLQ-C30对PROs进行评估。结果12个月后,阿米万他单抗化疗组77%的患者未出现症状进展,化疗组为60% (HR, 0.67; 95% CI, 0.46-0.98; p = 0.04)。两组患者的身体功能和总体健康状况均得到维持,阿米万他单化疗组患者在6个月和12个月时报告生活质量稳定或改善的比例更高。结论:savantamab联合化疗可显著延缓症状进展,且不影响与健康相关的生活质量,强化了其作为ex20in突变的非小细胞肺癌一线治疗的作用。
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引用次数: 0
Prognostic value of preoperative ctDNA and pathological venous invasion for recurrence in EGFR-mutated non-small cell lung cancer 术前ctDNA和病理性静脉浸润对egfr突变的非小细胞肺癌复发的预后价值
IF 4.4 2区 医学 Q1 ONCOLOGY Pub Date : 2026-03-01 Epub Date: 2025-11-04 DOI: 10.1016/j.lungcan.2025.108818
Yuya Murase , Hayato Koba , Hideharu Kimura , Isao Matsumoto , Tsukasa Ueda , Shunichi Nomura , Sachiko Arai , Nanao Terada , Liu Yifeng , Shigeki Nanjo , Yuichi Tambo , Takafumi Kobayashi , Satoshi Watanabe , Kenta Yamamura , Noriyuki Ohkura , Miki Abo , Akihiro Nomura , Seiji Yano

Introduction

Curative surgery followed by adjuvant osimertinib according to pathological stage (pStage) is standard for resectable epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). Nevertheless, recurrence remains a concern even in Stage IA, for which adjuvant osimertinib is not indicated. We evaluated the utility of circulating tumor DNA (ctDNA) to predict recurrence in patients with resected pStage I-III EGFR-mutated NSCLC and examined prognostic value of preoperative biomarkers and pathological features.

Methods

Between January 2017 and May 2020, 382 patients with lung tumors underwent surgery at Kanazawa University Hospital, including 88 with NSCLC harboring common EGFR mutations. Preoperative ctDNA was analyzed using droplet digital PCR, targeting EGFR mutations. Patients were followed for up to 6.4 years, and disease-free survival (DFS) and overall survival (OS) were evaluated.

Results

Preoperative ctDNA positivity was detected in 26.1 % and venous invasion in 39.8 %. ctDNA-positive patients had lower 60-month DFS (54.1 % vs. 84.1 %; HR = 3.25; 95 % CI, 1.13–9.21; p = 0.028) and 60-month OS (65.1 % vs. 95.9 %; HR = 6.10; 95 % CI, 1.11–33.46; p = 0.037). Venous invasion was independently associated with poorer DFS (HR = 8.73; 95 % CI, 1.81–41.93; p = 0.0068). In combined analyses, no recurrences occurred in the double-negative, whereas the double-positive had a lower 60-month DFS than the single-positive (HR = 3.61; 95 % CI, 1.19–10.93; p = 0.023).

Conclusion

Preoperative ctDNA detection and pathological venous invasion provide complementary prognostic information, and venous invasion is an independent predictor of recurrence risk in EGFR-mutated NSCLC. Combined assessment may refine postoperative risk stratification and inform perioperative management.
根据病理分期(pStage)进行根治性手术后辅以奥希替尼是可切除的表皮生长因子受体(EGFR)突变的非小细胞肺癌(NSCLC)的标准治疗方法。然而,即使在IA期,复发仍然是一个问题,辅助奥希替尼不适用。我们评估了循环肿瘤DNA (ctDNA)在预测切除的pi - iii期egfr突变的非小细胞肺癌患者复发中的应用,并检查了术前生物标志物和病理特征的预后价值。方法2017年1月至2020年5月,382例肺肿瘤患者在金泽大学医院接受了手术,其中88例患有常见EGFR突变的非小细胞肺癌。术前ctDNA分析采用液滴数字PCR,靶向EGFR突变。患者随访6.4年,评估无病生存期(DFS)和总生存期(OS)。结果术前ctDNA阳性占26.1%,静脉浸润占39.8%。ctdna阳性患者的60个月DFS(54.1%比84.1%;HR = 3.25; 95% CI, 1.13-9.21; p = 0.028)和60个月OS(65.1%比95.9%;HR = 6.10; 95% CI, 1.11-33.46; p = 0.037)较低。静脉侵犯与较差的DFS独立相关(HR = 8.73; 95% CI, 1.81 ~ 41.93; p = 0.0068)。在联合分析中,双阴性患者没有复发,而双阳性患者的60个月DFS低于单阳性患者(HR = 3.61; 95% CI, 1.19-10.93; p = 0.023)。结论术前ctDNA检测和病理性静脉浸润提供了互补的预后信息,静脉浸润是egfr突变NSCLC复发风险的独立预测因子。综合评估可细化术后风险分层,为围手术期管理提供信息。
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引用次数: 0
Immune-related disorders in patients with Thymic Epithelial Tumors: from pathogenesis to tailored interventions 胸腺上皮肿瘤患者的免疫相关疾病:从发病机制到量身定制的干预措施
IF 4.4 2区 医学 Q1 ONCOLOGY Pub Date : 2026-03-01 Epub Date: 2026-01-17 DOI: 10.1016/j.lungcan.2026.108915
Erica Pietroluongo , Giovannella Palmieri , Paolo Antonio Ascierto , Margaret Ottaviano

Background and objective

Thymic epithelial tumors (TETs) are rare malignancies often associated with immunological disorders (IDs), including autoimmune diseases and paraneoplastic syndromes. Myasthenia gravis (MG) is the most frequently reported condition, although other IDs can manifest across various organ systems. This review aims to give an overview of the current knowledge on the epidemiology, pathogenesis, and management of IDs associated with TETs, emphasizing their prognostic impact and challenges in clinical practice.

Methods

We performed a narrative review using PubMed and Embase databases to identify relevant literature published between January 1971 and October 2024. Keywords included “thymic epithelial tumors”, “immunological disorders,” “autoimmune diseases,” and “paraneoplastic syndromes.” Only peer-reviewed articles in English were included.

Key content and findings

This review examines the association of TETs with the most frequent IDs, including MG, pure red cell aplasia, and Good’s syndrome. The prognostic implications of IDs in TETs remain unclear, and the available literature presents conflicting data. While some studies suggest correlations with favourable outcomes, others fail to establish IDs as independent prognostic factors for recurrence-free survival (RFS) or overall survival (OS).

Conclusions

The management of TETs with associated IDs requires a multidisciplinary approach that integrates tumor-specific treatments and tailored interventions for immune-related disorders. Advances in understanding molecular mechanisms have shed light on their pathogenesis. Nevertheless, gaps persist regarding prognostic implications and long-term management. Future efforts should focus on identifying predictive biomarkers for immune complications, optimizing therapies, and enhancing international data collection to clarify the impact of IDs on patient outcomes.
背景和目的:胸腺上皮性肿瘤(TETs)是一种罕见的恶性肿瘤,通常与免疫性疾病(IDs)相关,包括自身免疫性疾病和副肿瘤综合征。重症肌无力(MG)是最常见的报道条件,尽管其他id可以表现在不同的器官系统。本文综述了与tet相关的IDs的流行病学、发病机制和管理方面的最新知识,强调了它们在临床实践中的预后影响和挑战。方法:我们使用PubMed和Embase数据库进行叙述性回顾,以确定1971年1月至2024年10月期间发表的相关文献。关键词包括“胸腺上皮肿瘤”、“免疫紊乱”、“自身免疫性疾病”和“副肿瘤综合征”。只收录了同行评议的英文文章。主要内容和发现:本综述探讨了tet与最常见的IDs(包括MG、纯红细胞发育不全和Good’s综合征)的关系。测试中id的预后含义尚不清楚,现有文献提供了相互矛盾的数据。虽然一些研究表明与有利结果相关,但其他研究未能将IDs作为无复发生存期(RFS)或总生存期(OS)的独立预后因素。结论:TETs与相关IDs的管理需要多学科的方法,结合肿瘤特异性治疗和针对免疫相关疾病的量身定制的干预措施。分子机制的研究进展揭示了其发病机制。然而,在预后影响和长期管理方面仍然存在差距。未来的努力应集中在确定免疫并发症的预测性生物标志物,优化治疗,并加强国际数据收集,以阐明id对患者预后的影响。
{"title":"Immune-related disorders in patients with Thymic Epithelial Tumors: from pathogenesis to tailored interventions","authors":"Erica Pietroluongo ,&nbsp;Giovannella Palmieri ,&nbsp;Paolo Antonio Ascierto ,&nbsp;Margaret Ottaviano","doi":"10.1016/j.lungcan.2026.108915","DOIUrl":"10.1016/j.lungcan.2026.108915","url":null,"abstract":"<div><h3>Background and objective</h3><div>Thymic epithelial tumors (TETs) are rare malignancies often associated with immunological disorders (IDs), including autoimmune diseases and paraneoplastic syndromes. Myasthenia gravis (MG) is the most frequently reported condition, although other IDs can manifest across various organ systems. This review aims to give an overview of the current knowledge on the epidemiology, pathogenesis, and management of IDs associated with TETs, emphasizing their prognostic impact and challenges in clinical practice.</div></div><div><h3>Methods</h3><div>We performed a narrative review using PubMed and Embase databases to identify relevant literature published between January 1971 and October 2024. Keywords included “thymic epithelial tumors”, “immunological disorders,” “autoimmune diseases,” and “paraneoplastic syndromes.” Only peer-reviewed articles in English were included.</div></div><div><h3>Key content and findings</h3><div>This review examines the association of TETs with the most frequent IDs, including MG, pure red cell aplasia, and Good’s syndrome. The prognostic implications of IDs in TETs remain unclear, and the available literature presents conflicting data. While some studies suggest correlations with favourable outcomes, others fail to establish IDs as independent prognostic factors for recurrence-free survival (RFS) or overall survival (OS).</div></div><div><h3>Conclusions</h3><div>The management of TETs with associated IDs requires a multidisciplinary approach that integrates tumor-specific treatments and tailored interventions for immune-related disorders. Advances in understanding molecular mechanisms have shed light on their pathogenesis. Nevertheless, gaps persist regarding prognostic implications and long-term management. Future efforts should focus on identifying predictive biomarkers for immune complications, optimizing therapies, and enhancing international data collection to clarify the impact of IDs on patient outcomes.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"213 ","pages":"Article 108915"},"PeriodicalIF":4.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146029993","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
Methodological considerations in assessing the clinical impact of TP53 classifications in advanced NSCLC 评估晚期非小细胞肺癌TP53分类的临床影响的方法学考虑
IF 4.4 2区 医学 Q1 ONCOLOGY Pub Date : 2026-03-01 Epub Date: 2026-01-23 DOI: 10.1016/j.lungcan.2026.108937
Xiaorong Lu, Shanshan Yuan
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引用次数: 0
期刊
Lung Cancer
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