Clinical lung cancer最新文献_第3页

Treatment Patterns and Clinical Outcomes in Patients With EGFR-Mutated Non–Small-Cell Lung Cancer After Progression on Osimertinib 表皮生长因子受体突变的非小细胞肺癌患者在奥希替尼治疗进展后的治疗模式和临床疗效。

IF 3.3 3区医学 Q2 ONCOLOGY

Clinical lung cancer

Pub Date : 2025-01-01 DOI: 10.1016/j.cllc.2024.09.006

Nathaniel D. Robinson , Maureen E. Canavan , Peter L. Zhan , Brooks V. Udelsman , Ranjan Pathak , Daniel J. Boffa , Sarah B. Goldberg

Introduction

For patients with advanced epidermal growth factor receptor (EGFR)-mutated non–small-cell lung cancer (NSCLC) who progress on first-line osimertinib, the optimal second-line treatment regimen after progression is not known. We sought to assess practice patterns and evaluate the association between different therapies and survival in patients with EGFR-mutated NSCLC following progression on first-line osimertinib.

Methods

Retrospective cohort study of patients who received first-line treatment with osimertinib using a population-based, multicenter nationwide electronic health record-derived deidentified database.

Results

We identified 2373 patients who received first-line osimertinib. The majority (n = 2279) received osimertinib monotherapy. A total of 538 patients received first-line osimertinib and had second-line treatment data available. Second-line treatment regimens were varied: 65% (n = 348) included chemotherapy, 37% (n = 197) included an immune checkpoint inhibitor (ICI), and 44% (n = 234) included an EGFR tyrosine kinase inhibitor (TKI).

We then analyzed the 333 patients with performance status 0-2 who received chemotherapy with osimertinib (n = 107, 32%) versus chemotherapy without osimertinib (n = 226, 68%). The continuation of osimertinib with chemotherapy was associated with superior progression-free survival (PFS; median: 10.1 versus 5.9 months, Hazard Ratio [HR]: 0.48, 95% Confidence Interval [CI]: [0.34, 0.68], P < .001) and overall survival (OS; median: 17.0 versus 12.8 months, HR: 0.64, 95% CI: [0.44, 0.93], P = .018) compared to other chemotherapy approaches without osimertinib. This effect was most pronounced in patients with an EGFR exon 19 deletion.

Conclusions

Following progression on osimertinib, a wide variety of treatment regimens were used. The continuation of osimertinib with chemotherapy in the second line was associated with increased PFS and OS.

简介晚期表皮生长因子受体（EGFR）突变非小细胞肺癌（NSCLC）患者在一线奥希替尼治疗后病情进展，但进展后的最佳二线治疗方案尚不清楚。我们试图评估EGFR突变的NSCLC患者在一线奥希替尼治疗进展后的治疗模式，并评估不同疗法与生存期之间的关联：使用基于人群的多中心全国性电子健康记录衍生去标识数据库，对接受奥希替尼一线治疗的患者进行回顾性队列研究：我们确定了2373名接受奥希替尼一线治疗的患者。大多数患者（n = 2279）接受了奥希替尼单药治疗。共有538名患者接受了奥希替尼一线治疗，并有二线治疗数据。二线治疗方案多种多样：65%（n = 348）采用化疗，37%（n = 197）采用免疫检查点抑制剂（ICI），44%（n = 234）采用表皮生长因子受体酪氨酸激酶抑制剂（TKI）。然后，我们分析了333名表现状态为0-2的患者接受奥希替尼化疗（107人，32%）与不接受奥希替尼化疗（226人，68%）的对比情况。在化疗的同时继续使用奥希替尼可获得更好的无进展生存期（PFS，中位数为 10.1 对 5.9）：中位数：10.1 个月对 5.9 个月，危险比 [HR]：0.48, 95% Confidence Interval [CI]：[0.34，0.68]，P < .001）和总生存期（OS；中位数：17.0 个月对 12.8 个月）：17.0个月对12.8个月，HR：0.64，95% CI：[0.44，0.93]，P = .018）。这种效应在表皮生长因子受体外显子19缺失的患者中最为明显：结论：奥希莫替尼治疗进展后，采用了多种治疗方案。结论：奥希莫替尼治疗进展后，采用了多种治疗方案，在二线治疗中继续使用奥希替尼并进行化疗与延长PFS和OS有关。

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引用次数: 0

Comment on ``Prognostic Impact of TP53 Mutations in Metastatic Nonsquamous Non-small-cell Lung Cancer'' 关于 "TP53突变对转移性非鳞状非小细胞肺癌的诊断影响 "的评论。

IF 3.3 3区医学 Q2 ONCOLOGY

Clinical lung cancer

Pub Date : 2025-01-01 DOI: 10.1016/j.cllc.2024.10.011

Laurent Mathiot, Judith Raimbourg

引用次数: 0

A Poor Prognostic ALK Phenotype: A Review of Molecular Markers of Poor Prognosis in ALK Rearranged Nonsmall Cell Lung Cancer 预后不良的 ALK 表型：ALK重排非小细胞肺癌预后不良的分子标志物综述。

IF 3.3 3区医学 Q2 ONCOLOGY

Clinical lung cancer

Pub Date : 2025-01-01 DOI: 10.1016/j.cllc.2024.10.009

Sze  Wah  Samuel Chan , Joy Zeng , Jack Young , Samir  H. Barghout , Faisal Al-Agha , Stavroula Raptis , M.  Catherine Brown , Geoffrey Liu , Rosalyn Juergens , Kevin Jao

Background

Patients with nonsmall cell lung cancer with anaplastic lymphoma kinase (ALK) rearrangements derive a significant and durable clinical benefit from tyrosine kinase inhibitors (TKIs). However, early progression/death on treatment occurs in a subset of patients, which we term the poor prognostic ALK phenotype. This review aims to summarize the known molecular mechanisms that underlie this phenotype with a focus on variant 3 and TP53 mutations.

Methods

A scoping review was performed using scientific databases such as Ovid Medline, Ovid Embase, and Cochrane Central Register of Controlled Trials. Studies included molecular markers of poor prognosis, with a focus on TP53 mutations, variant 3 re-arrangements, and poor clinical response to TKIs.

Results

Of 4371 studies screened, 108 were included. Numerous studies implicated a negative prognostic role of variant 3, likely mediated through the acquisition of on-target resistance mutations and TP53 mutations which are associated with greater chromosomal instability and mutational burden. Co-occurring variant 3 and TP53 mutations were associated with even worse survival. Other mediators of early resistance development include aberrations in cell cycle regulators and mutations in cell signaling pathways. Comprehensive genomic analysis from first-line TKI clinical trial data was unable to identify a singular genomic signature that underlies the poor prognostic phenotype but implicated a combination of pathways.

Conclusions

This scoping review highlights that the poor prognostic ALK phenotype is likely composed of a heterogeneous variety of genomic factors. There remains an unmet need for a genomic assay to integrate these various molecular markers to predict this ALK phenotype.

背景：患有无性淋巴瘤激酶（ALK）重排的非小细胞肺癌患者可从酪氨酸激酶抑制剂（TKIs）中获得显著而持久的临床获益。然而，有一部分患者会在治疗过程中出现早期进展/死亡，我们称之为预后不良的ALK表型。本综述旨在总结导致这种表型的已知分子机制，重点关注变异3和TP53突变：方法：使用 Ovid Medline、Ovid Embase 和 Cochrane Central Register of Controlled Trials 等科学数据库进行了范围界定综述。研究内容包括预后不良的分子标志物，重点是TP53突变、变异3重排以及对TKIs的不良临床反应：在筛选出的 4371 项研究中，有 108 项被纳入。大量研究表明，变异体3对预后有负面作用，可能是通过获得靶上耐药突变和TP53突变介导的，而TP53突变与更大的染色体不稳定性和突变负荷有关。同时出现变异3和TP53突变与更差的生存率有关。早期耐药性产生的其他因素包括细胞周期调节因子的畸变和细胞信号通路的突变。从一线TKI临床试验数据中进行的综合基因组分析无法确定导致预后不良表型的单一基因组特征，而是涉及多种途径：本次范围界定综述强调，预后不良的ALK表型可能由各种不同的基因组因素组成。目前仍需要一种基因组检测方法来整合这些不同的分子标记物，以预测这种 ALK 表型。

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引用次数: 0

Comment on “Prognostic Impact of TP53 Mutations in Metastatic Nonsquamous Non-Small-Cell Lung Cancer” 就 "TP53 基因突变对转移性非鳞状非小细胞肺癌的预后影响 "发表评论。

IF 3.3 3区医学 Q2 ONCOLOGY

Clinical lung cancer

Pub Date : 2025-01-01 DOI: 10.1016/j.cllc.2024.10.010

Rameez Qasim , Zahra Riaz

引用次数: 0

Comparison of Long-Term Survival Between Robotic and Video-Assisted Lobectomy for Stage Ⅰ NSCLC With Radiologic Solid Tumors: A Propensity Score Matching Study 机器人和视频辅助肺叶切除术治疗Ⅰ期NSCLC伴放射性实体瘤的长期生存率比较：倾向得分匹配研究》。

IF 3.3 3区医学 Q2 ONCOLOGY

Clinical lung cancer

Pub Date : 2025-01-01 DOI: 10.1016/j.cllc.2024.10.004

Jianfeng Zhang , Zhongjie Wang , Yuming Wang , Xuewen Yu , Yanpen Liang , Changbo Sun , Qianjun Zhou

Background

To compare the long-term survival between robotic and video-assisted thoracic surgery (VATS) lobectomy for stage Ⅰ non–small-cell lung cancer (NSCLC) with radiologic solid tumors.

Methods

Clinical stage Ⅰ NSCLC patients with radiologic solid tumors who underwent robotic-assisted thoracic surgery (RATS) or VATS lobectomy between 2015 and 2017 were retrospectively reviewed. A propensity score matching analysis was performed to balance the baseline characteristics. The primary end points were overall survival (OS) and recurrence-free survival (RFS).

Results

A total of 518 patients (225 RATS and 293 VATS) were included. After propensity score matching, there were 170 cases in each group. Patients undergoing RATS had shorter operative time than VATS (98.12 min vs. 112.26 min; P < 0.001). The RATS approach resulted in a higher number of resected lymph nodes (LNs) (11.75 vs. 9.77; P < 0.001). The postoperative complication rates were comparable (7.6% vs. 10.0%, P = .566). The rates of 5-year OS and RFS for the RATS and VATS were 92% versus 89% (P = .62) and 82% vs. 86% (P = .70), respectively. Multivariate analysis revealed that the number of resected LNs was significantly associated with overall survival (OR = 1.94 [95% confidence interval [CI]: 1.07-3.51], P = .029).

Conclusion

The long-term survival outcomes of RATS and VATS are similar for c-stage Ⅰ NSCLC with radiologic solid tumors. The use of robotics is associated with more lymph node dissection and shorter operative time. We suggested that the number of examined lymph nodes rather than surgical approaches was associated with overall survival.

研究背景比较机器人和视频辅助胸腔手术（VATS）肺叶切除术治疗Ⅰ期非小细胞肺癌（NSCLC）放射性实体瘤的长期生存率：对2015年至2017年间接受机器人辅助胸腔手术（RATS）或VATS肺叶切除术的放射性实体瘤临床Ⅰ期NSCLC患者进行回顾性研究。为平衡基线特征，进行了倾向评分匹配分析。主要终点为总生存期（OS）和无复发生存期（RFS）：结果：共纳入 518 例患者（225 例 RATS 和 293 例 VATS）。经过倾向评分匹配后，每组各有 170 例。与 VATS 相比，RATS 患者的手术时间更短（98.12 分钟对 112.26 分钟；P < 0.001）。RATS方法切除的淋巴结（LN）数量更高（11.75 对 9.77；P < 0.001）。术后并发症发生率相当（7.6% 对 10.0%，P = .566）。RATS和VATS的5年OS和RFS率分别为92%对89%（P = .62）和82%对86%（P = .70）。多变量分析显示，切除的LN数量与总生存率显著相关（OR = 1.94 [95% 置信区间 [CI]：1.07-3.51]，P = .029）：结论：对于伴有放射性实体瘤的c期ⅠNSCLC，RATS和VATS的长期生存结果相似。使用机器人与更多的淋巴结清扫和更短的手术时间相关。我们认为，检查淋巴结的数量而非手术方式与总生存率有关。

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引用次数: 0

Histologic Transformation of ALK-Rearranged Lung Adenocarcinomas to High-Grade LCNEC: Clinical and Molecular Description of Three Cases alk重排肺腺癌向高级别LCNEC的组织学转化：3例临床和分子描述。

IF 3.3 3区医学 Q2 ONCOLOGY

Clinical lung cancer

Pub Date : 2025-01-01 DOI: 10.1016/j.cllc.2024.11.012

Paolo Ambrosini , Daniela Miliziano , Giorgia Di Liberti , Daniele Lorenzini , Silvia Marchesi , Anna Bassetti , Elena Tamborini , Rita Leporati , Teresa Beninato , Laura Mazzeo , Marta Brambilla , Monica Ganzinelli , Arsela Prelaj , Claudia Proto , Filippo Guglielmo De Braud , Giuseppe Lo Russo , Mario Occhipinti

•
Anaplastic lymphoma kinase (ALK) rearrangements occur in 3-5% of non-small cell lung cancer (NSCLC) cases, with high sensitivity to ALK-tyrosine kinase inhibitors (TKIs) like alectinib, brigatinib, lorlatinib, and ensartinib. Resistance to tehse treatments is common and nearly inevitable, driven by genetic alterations and histologic transformations, notably to small cell lung carcinoma (SCLC).
•
In the present series, we describe a rare resistance mechanism in three cases of ALK-rearranged NSCLC transforming into high-grade large cell neuroendocrine carcinoma (LCNEC) after ALK-TKI treatment. These patients exhibited both histologic transformation and on-target ALK mutations, such as L1196M, D1203N, and L1198F, emphasizing the dual resistance mechanisms.
•
The identification of LCNEC transformation as a resistance mechanism emphasizes the importance of individualizing treatment strategies. The clinical outcomes of LCNEC-transformed cases varied, with some patients responding poorly to chemotherapy, underscoring the aggressive nature of this transformation. Regular tissue re-biopsies at disease progression can guide therapy choices by identifying resistance mechanisms. Liquid biopsies can serve as an alternative for monitoring molecular resistance in situations where tissue biopsies are not attainable. These findings advocate for an adaptive treatment approach, integrating molecular and histologic evaluations to optimize outcomes for patients with ALK-rearranged NSCLC.

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引用次数: 0

Perioperative Outcomes of Neoadjuvant Therapy in Resectable Lung Cancer Patients With Endobronchial Disease in the Era of Personalized Medicine 个性化医疗时代可切除肺癌患者支气管内疾病的新辅助治疗围手术期疗效。

IF 3.3 3区医学 Q2 ONCOLOGY

Clinical lung cancer

Pub Date : 2025-01-01 DOI: 10.1016/j.cllc.2024.10.003

Joseph Seitlinger , Devangi Patel , Andrew Meng , Luciano Bulgarelli-Maqueda , Jonathan Cools-Lartigue , Christian Sirois , Lorenzo Ferri , Jonathan Spicer , Sara Najmeh

<div><h3>Background</h3><div>Lung cancer remains the leading cause of cancer-related deaths worldwide. Recent studies have highlighted the benefit of neo-adjuvant therapies in the treatment of resectable stage IB to IIIA cases which will likely increase the use of neoadjuvant therapies (NAT) across multiple stages, both earlier and later. This includes the combination of chemotherapy and immunotherapy as well as the more widespread use of targeted therapies with or without the addition of radiation.</div><div>This heterogenous group of resectable tumors includes proximal tumors with different levels of endobronchial involvement and secondary distal atelectasis and sometimes superimposed infections which adds a level of concern and complexity when using NAT. In this study, we evaluate the prevalence of endobronchial lesions in patients treated with NAT, as well as the rate of associated complications.</div></div><div><h3>Patients and Methods</h3><div>Data was obtained from a prospectively maintained thoracic surgery database, the Thoracic Oncology Clinical Database and Biobank. Patients with proven clinical stage II-III NSCLC that underwent resection within the Division of Thoracic Surgery at the McGill University Health Centre (Montreal, QC, Canada) from January 2015 to December 2020 were included.</div><div>Chest computed tomography scans prior to neoadjuvant therapy were reviewed by 2 senior thoracic surgeons to establish the presence of an endobronchial tumor lesion. The presence of an endobronchial lesion was defined by a tumoral lesion obstructing a bronchus or several bronchi AND responsible for lung atelectasis distally (with at least 1 occluded segment). Treatment-related and postoperative complications were collected retrospectively by reviewing patient charts.</div></div><div><h3>Results</h3><div>Overall, 110 patients met the inclusion criteria, of which 37/110 patients had endobronchial lesions before starting neoadjuvant therapy (33.6%). These patients had a higher rate of global complications 23/37 (62.2%) during neoadjuvant treatment compared to patients without obstruction 30/73 (41.1%) (<em>P</em> = .04). There was no difference in terms of severity of complications between the 2 groups (<em>P</em> = .34). The group with endobronchial lesions was found to have an increased rate of pulmonary complications, of which there were none in the other group (5/37, 13.5% vs. 0/73, 0%, <em>P</em> = .004). There were 2 cases of patients requiring urgent surgeries before completing NAT due to pulmonary complications in the endobronchial lesion group (2/37, 5.4%) and none in the group without obstruction.</div></div><div><h3>Conclusion</h3><div>Patients who are treated with NAT for locally advanced resectable lung cancer usually have larger tumors, where it is not uncommon to encounter endobronchial lesions responsible for downstream obstruction. In this study, the prevalence of endobronchial lesions was found to be 1 third of the patients unde

背景：肺癌仍然是全球癌症相关死亡的主要原因。最近的研究强调了新辅助疗法在治疗可切除的 IB 期至 IIIA 期病例中的益处，这可能会增加新辅助疗法（NAT）在多个分期（包括早期和晚期）中的使用。这包括化疗和免疫疗法的结合，以及靶向疗法在放疗或不放疗情况下的更广泛应用。这组可切除肿瘤的异质性包括不同程度的支气管内膜受累的近端肿瘤、继发性远端肺不张以及有时叠加的感染，这增加了使用 NAT 时的担忧和复杂性。在这项研究中，我们评估了接受 NAT 治疗的患者中支气管内病变的发生率以及相关并发症的发生率：数据来自一个前瞻性维护的胸外科数据库、胸部肿瘤临床数据库和生物库。纳入了2015年1月至2020年12月期间在麦吉尔大学健康中心（加拿大昆士兰州蒙特利尔市）胸外科接受切除术的已确诊临床II-III期NSCLC患者。新辅助治疗前的胸部计算机断层扫描由两名资深胸外科医生进行审查，以确定是否存在支气管内肿瘤病变。支气管内肿瘤病变的定义是肿瘤病变阻塞了一条支气管或数条支气管，并导致远端肺不张（至少有一段闭塞）。通过查看患者病历回顾性地收集了与治疗相关的并发症和术后并发症：共有 110 例患者符合纳入标准，其中 37/110 例患者在开始新辅助治疗前有支气管内病变（33.6%）。与无梗阻的患者30/73（41.1%）相比，这些患者在新辅助治疗期间的总体并发症发生率更高，为23/37（62.2%）（P = .04）。两组患者的并发症严重程度没有差异（P = .34）。发现支气管内病变组的肺部并发症发生率增加，而另一组则没有（5/37，13.5% vs. 0/73，0%，P = .004）。支气管内病变组有2例患者在完成NAT治疗前因肺部并发症而需要进行紧急手术（2/37，5.4%），而无梗阻组则没有：结论：接受NAT治疗的局部晚期可切除肺癌患者通常肿瘤较大，遇到支气管内病变导致下行阻塞的情况并不少见。本研究发现，接受 NAT 治疗的患者中有三分之一存在支气管内病变。支气管内病变的存在与新辅助治疗期间并发症风险的增加有关。这些并发症更多地表现为肺部并发症，在某些情况下需要紧急手术切除。因此，接受新辅助治疗的支气管内肿瘤患者应被确定为高危人群，并可能从更密切的临床随访中获益。

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引用次数: 0

Participation in Non-small Cell Lung Cancer Clinical Trials in the United States by Race/Ethnicity 按种族/族裔分列的美国非小细胞肺癌临床试验参与情况。

IF 3.3 3区医学 Q2 ONCOLOGY

Clinical lung cancer

Pub Date : 2025-01-01 DOI: 10.1016/j.cllc.2024.09.009

Meghann Wheeler , Shama Karanth , Joel Divaker , Hyung-Suk Yoon , Jae Jeong Yang , Maisey Ratcliffe , Marissa Blair , Hiren J Mehta , Mindaugas Rackauskas , Dejana Braithwaite

Introduction

Despite efforts by Cancer Centers and community organizations to increase diversity in clinical trials, significant racial/ethnic disparities remain. Given the high mortality rates in non-small cell lung cancer (NSCLC), it is important to increase diversity in NSCLC trials, ensuring all patients benefit from advances in new treatment modalities.

Materials and Methods

We evaluated the distribution of racial/ethnic minority enrollment in NSCLC clinical trials using data from ClinicalTrials.gov. We extracted trial characteristics, including start year, study phase, tumor stage, sample size, sponsor, geographic region, and masking. The number of participants by race/ethnicity was obtained from ClinicalTrials.gov or linked publications. Using annual NSCLC incidence data from SEER*Stat for each racial/ethnic group from 2010 to 2019, we applied a 2-sample test for equality of proportions with continuity correction to assess differences between incidence and trial participation.

Results

A total of 147 unique studies were included in the final analysis. Of the 28,540 participants, 79.6% were White, with 3% Black, 10.4% Asian or Pacific Islander and 3.4% Hispanic/Latino. Most participants were enrolled in phase III trials (63.8%), industry-sponsored (93.9%), and open-label (67.7%). Black patients were more commonly enrolled in academic sponsored trials and less commonly enrolled in masked (i.e., blinded) studies. When comparing trial participation to annual incidence data, we observed underrepresentation among Black participants (Difference: −7.9%) and Hispanic/Latino participants (Difference: −3.2%).

Conclusion

Persistent underrepresentation exists in NSCLC clinical trials among Black and Hispanic/Latino patients. We urge further investigation of these findings through well-designed clinical trials among diverse patient populations.

导言：尽管癌症中心和社区组织努力提高临床试验的多样性，但种族/民族差异仍然很大。鉴于非小细胞肺癌（NSCLC）的高死亡率，提高NSCLC试验的多样性非常重要，这样才能确保所有患者都能受益于新治疗模式的进步：我们利用ClinicalTrials.gov的数据评估了NSCLC临床试验中少数种族/人种入组的分布情况。我们提取了试验特征，包括开始年份、研究阶段、肿瘤分期、样本大小、赞助商、地理区域和掩蔽。按种族/民族划分的参与者人数来自 ClinicalTrials.gov 或链接的出版物。利用SEER*Stat提供的2010年至2019年各种族/族裔群体的NSCLC年度发病率数据，我们采用了带连续性校正的2样本比例相等检验来评估发病率与试验参与度之间的差异：共有 147 项独特的研究被纳入最终分析。在 28,540 名参与者中，79.6% 为白人，3% 为黑人，10.4% 为亚洲人或太平洋岛民，3.4% 为西班牙裔/拉丁美洲人。大多数参与者参加了 III 期试验（63.8%）、行业资助试验（93.9%）和开放标签试验（67.7%）。黑人患者更常参加学术赞助的试验，而较少参加蒙面（即盲法）研究。在将试验参与情况与年度发病率数据进行比较时，我们观察到黑人参与者（差异：-7.9%）和西班牙裔/拉丁裔参与者（差异：-3.2%）的代表性不足：结论：黑人和西班牙裔/拉丁美洲裔患者在 NSCLC 临床试验中的代表性持续不足。我们敦促通过在不同患者群体中进行精心设计的临床试验来进一步研究这些发现。

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引用次数: 0

Randomized Phase II Trial of Amrubicin Plus Irinotecan Versus Cisplatin Plus Irinotecan in Chemo-naïve Patients With Extensive-Disease Small-Cell Lung Cancer: Results of the Japan Multinational Trial Organization (JMTO) LC 08-01 在化疗无效的重症小细胞肺癌患者中开展氨柔比星加伊立替康与顺铂加伊立替康的随机 II 期试验：日本多国试验组织 (JMTO) LC 08-01 的结果。

IF 3.3 3区医学 Q2 ONCOLOGY

Clinical lung cancer

Pub Date : 2025-01-01 DOI: 10.1016/j.cllc.2024.09.004

Hiroshige Yoshioka , Tadashi Ishida , Shinji Atagi , Akihiro Tamiya , Takashi Nishimura , Yasuo Iwamoto , Masashi Kanehara , Young Hak Kim , Yohei Korogi , Keisuke Tomii , Nobuyuki Katakami , Kiyoshi Komuta , Masanori Nishikawa , Akihiko Gemma , Kenichi Yamaki , Masaaki Kawahara , Chisato Miyakoshi , Tadashi Mio

Background

We conducted a randomize phase II study to evaluate the efficacy and safety of topoisomerase II inhibitor amrubicin plus topoisomerase I inhibitor irinotecan (AI) compared with cisplatin plus irinotecan (PI) as first-line therapy in patients with extensive-disease (ED) small-cell lung cancer (SCLC).

Patients and Methods

Chemo-naïve patients with pathologically proven ED-SCLC (including limited disease (LD) SCLC with malignant effusion) were enrolled. Patients were randomized 1:1 to receive either AI (amrubicin 90mg/m² on day 1 and irinotecan 50mg/m² on days 1 and 8 of a 21-day cycle) or PI (cisplatin 60mg/m² on day 1 and irinotecan 60mg/m² on days 1, 8 and 15 of a 28-day cycle). The primary endpoint was overall survival proportion at 1 year.

Results

A total of 100 patients were randomly assigned to AI (n = 50) or to PI (n = 50). The 1-year overall survival proportions were 68.0% (95% confidence interval (CI): 56.2-82.2%) for AI and 59.2% (46.9-74.7%) for PI (1-sided P = .18). Median survival time was 14.8 months for AI and 13.5 months for PI with a hazard ratio (HR) of 0.618 (0.398-0.961, stratified log-rank test P = .031). Median progression-free survival time was 4.8 months for AI and 5.4 months for PI (stratified log-rank test, P = .54). Objective response rate was 70.0% (55.4-82.1%) for AI and 55.1% (40.2-69.3%) for PI (Fisher exact test, P = .15). There was no significant difference in hematological toxicity, whereas rates of vomiting, loss of appetite, diarrhea, and elevated serum creatinine are more frequent in PI. Interstitial lung disease (Grade 2 or 3) developed in 5 patients in AI and in 1 patient in PI. There was no treatment-related death.

Conclusion

Although the study did not meet its primary endpoint, AI showed promising efficacy and good tolerability in chemo-naïve patients with ED-SCLC.

研究背景我们进行了一项随机II期研究，评估拓扑异构酶II抑制剂阿鲁必钦加拓扑异构酶I抑制剂伊立替康（AI）与顺铂加伊立替康（PI）作为广泛病变（ED）小细胞肺癌（SCLC）患者一线治疗的有效性和安全性：患者：病理证实为ED-SCLC（包括伴有恶性渗出的局限性疾病（LD）SCLC）的化疗无效患者。患者按1:1随机分配接受AI（阿鲁比星90毫克/平方米，第1天；伊立替康50毫克/平方米，第1天和第8天，21天为一个周期）或PI（顺铂60毫克/平方米，第1天；伊立替康60毫克/平方米，第1天、第8天和第15天，28天为一个周期）治疗。主要终点是1年的总生存率：共有100名患者被随机分配接受AI治疗（50人）或PI治疗（50人）。AI 的 1 年总生存率为 68.0%（95% 置信区间 (CI)：56.2-82.2%），PI 为 59.2%（46.9-74.7%）（单侧 P = .18）。AI 的中位生存时间为 14.8 个月，PI 为 13.5 个月，危险比 (HR) 为 0.618（0.398-0.961，分层对数秩检验 P = .031）。AI 的中位无进展生存期为 4.8 个月，PI 为 5.4 个月（分层对数秩检验，P = .54）。AI的客观反应率为70.0%（55.4-82.1%），PI为55.1%（40.2-69.3%）（费雪精确检验，P = .15）。血液学毒性方面没有明显差异，而呕吐、食欲不振、腹泻和血清肌酐升高在 PI 中更为常见。5 名 AI 患者和 1 名 PI 患者出现间质性肺病（2 级或 3 级）。没有出现与治疗相关的死亡病例：尽管研究未达到主要终点，但AI在化疗无效的ED-SCLC患者中显示出良好的疗效和耐受性。

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引用次数: 0

Inclusion of Surgery in Multimodality Treatment is Predictive of Better Survival in Stage IIIA Non-small Cell Lung Cancer: An Inverse Probability Treatment-Weighting Analysis 将手术纳入多模式治疗可提高 IIIA 期非小细胞肺癌患者的生存率：逆概率治疗权重分析》。

IF 3.3 3区医学 Q2 ONCOLOGY

Clinical lung cancer

Pub Date : 2025-01-01 DOI: 10.1016/j.cllc.2024.10.007

Feitong Lei , Janeesh Sekkath-Veedu , Bin Huang , Quan Chen , Mansi Shah-Jadeja , Thomas E. Stinchcombe , Zhonglin Hao

Introduction

Stage IIIA non-small cell lung cancers (NSCLC) are treated with surgery-based multimodality approach or definitive chemoradiation therapy plus durvalumab consolidation. It is not clear whether surgery-based multimodality therapy has any survival advantage over definitive chemoradiation plus immunotherapy consolidation.

Method

National Cancer Database (NCDB) was used to identify NSCLC patients at stage IIIA (AJCC8, T3N1/T4N0-1 or T1N2/T2N2) who are treated with surgery-based multimodality approach or definitive chemoradiation plus durvalumab. Survival between groups were compared using inverse probability treatment weighting (IPTW)-adjusted Kaplan Meier curves and Cox proportional hazards regression analysis. Results were independently confirmed by Landmark Inverse and Clone Censor Weight analyses to address immortal time bias.

Results

From 2017 to 2019, 24,170 patients are identified as potentially resectable stage IIIA (T3N1, T4N0-1, T1N2/T2N2). Among them, 2,615 (10.8%) received surgery-based multimodality therapy and 2,985 (12.4%) received definitive chemoradiation plus durvalumab. Surgery based multimodality approach had significant survival advantage over definitive chemoradiation plus durvalumab (HR 0.74; 95% CI 0.69-0.79, P < .001). The median overall survival (mOS) for the definitive chemoradiation plus durvalumab group was 48.59 m whereas mOS was not reached for surgery-based multimodality group. This trend persisted in both N2 negative and positive tumors. Neoadjuvant chemotherapy was just as effective as adjuvant chemotherapy and delay of immunotherapy consolidation to 12 weeks after initiation of chemoradiation did not negatively affect survival outcome.

Conclusion

For stage IIIA NSCLC patients, surgery-based multimodality treatment outperformed chemoradiation plus durvalumab in survival.

简介IIIA期非小细胞肺癌(NSCLC)采用基于手术的多模式疗法或明确的化放疗加durvalumab巩固治疗。目前尚不清楚以手术为基础的多模式疗法与明确的化学放疗加免疫疗法巩固疗法相比是否具有生存优势：方法：利用美国国家癌症数据库（NCDB）来识别IIIA期（AJCC8，T3N1/T4N0-1或T1N2/T2N2）的NSCLC患者，这些患者接受了基于手术的多模式疗法或确定性化疗加杜瓦单抗疗法。采用经反概率治疗加权（IPTW）调整的卡普兰-梅耶曲线和考克斯比例危险回归分析比较各组间的生存率。结果由地标逆向分析和克隆检查权重分析独立确认，以解决不死时间偏倚问题：从2017年到2019年，24170名患者被确定为潜在可切除IIIA期（T3N1、T4N0-1、T1N2/T2N2）。其中，2615 人（10.8%）接受了基于手术的多模式治疗，2985 人（12.4%）接受了明确的化疗加杜伐单抗治疗。与明确的化疗加杜瓦单抗相比，基于手术的多模式疗法具有显著的生存优势（HR 0.74；95% CI 0.69-0.79，P < .001）。确定性化疗加杜伐单抗组的中位总生存期（mOS）为48.59米，而基于手术的多模式组未达到mOS。这一趋势在N2阴性和阳性肿瘤中都持续存在。新辅助化疗与辅助化疗同样有效，免疫疗法巩固治疗延迟至开始化疗后12周并不会对生存结果产生负面影响：结论：对于IIIA期NSCLC患者，以手术为基础的多模式治疗在生存率方面优于化疗加durvalumab治疗。

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