评估多西他赛在KRAS g12c突变的NSCLC中的有效性：来自真实世界队列的见解

IF 4.4 2区医学 Q1 ONCOLOGY

Lung Cancer Pub Date : 2025-09-24 DOI:10.1016/j.lungcan.2025.108768

Matthias Scheffler , Lia Tzala , Karly Louie , Thorsten Persigehl , Simon Lennartz , Katarina Öhrling , Julia Gehrman , Lea Ruge , Felix John , Anna Rasokat , Anna Kron , Michaela Potzner , Sabine Merkelbach-Bruse , Reinhard Buettner , Udo Siebolts , Jürgen Wolf

{"title":"评估多西他赛在KRAS g12c突变的NSCLC中的有效性：来自真实世界队列的见解","authors":"Matthias Scheffler , Lia Tzala , Karly Louie , Thorsten Persigehl , Simon Lennartz , Katarina Öhrling , Julia Gehrman , Lea Ruge , Felix John , Anna Rasokat , Anna Kron , Michaela Potzner , Sabine Merkelbach-Bruse , Reinhard Buettner , Udo Siebolts , Jürgen Wolf","doi":"10.1016/j.lungcan.2025.108768","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Specific <em>KRAS</em> G12C inhibitors have reached the stage of targeted therapy for non-small cell lung cancer (NSCLC). However, there is a dearth of real-world data in the context of immune checkpoint blockade and docetaxel effectiveness in NSCLC patients with <em>KRAS</em> G12C mutations. This study was designed to address this gap in knowledge by analyzing a real-world cohort of patients with <em>KRAS</em> G12C mutations treated with docetaxel in the era of immune-checkpoint-blockade availability.</div></div><div><h3>Patients and Methods</h3><div>The Network Genomic Medicine (NGM) database was queried to identify patients with <em>KRAS</em> G12C mutations who had been treated with docetaxel monotherapy or combinations between July 1st, 2015, and December 31st, 2019.</div></div><div><h3>Results</h3><div>The median rwOS was 7.6 months (95 % CI: 6.5–14.5), with improved outcomes observed for docetaxel plus nintedanib (10.4 months) compared to docetaxel monotherapy (6.5 months). The rwPFS was 3.4 months overall, with combination therapy showing marginally superior efficacy (4.3 vs. 2.2 months). The presence of concomitant mutations in <em>STK11</em> and <em>KEAP1</em> was associated with inferior outcomes, whereas elevated PD-L1 expression was associated with enhanced rwOS. Notably, the inclusion of patients with ECOG 2 or higher underscored the unfavorable outcomes observed in this subgroup, which is typically excluded from pivotal trials.</div></div><div><h3>Conclusion</h3><div>The effectiveness of docetaxel, administered with or without antiangiogenic agents, was found to be limited in a real-world setting of non-small cell lung cancer (NSCLC) patients with a <em>KRAS</em> G12C mutation, emphasizing the need for novel therapies. Comprehensive molecular profiling remains crucial for optimizing treatment outcomes in this heterogeneous subgroup.</div></div>","PeriodicalId":18129,"journal":{"name":"Lung Cancer","volume":"209 ","pages":"Article 108768"},"PeriodicalIF":4.4000,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Evaluating docetaxel effectiveness in KRAS G12C-mutated NSCLC: insights from a Real-World cohort\",\"authors\":\"Matthias Scheffler , Lia Tzala , Karly Louie , Thorsten Persigehl , Simon Lennartz , Katarina Öhrling , Julia Gehrman , Lea Ruge , Felix John , Anna Rasokat , Anna Kron , Michaela Potzner , Sabine Merkelbach-Bruse , Reinhard Buettner , Udo Siebolts , Jürgen Wolf\",\"doi\":\"10.1016/j.lungcan.2025.108768\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>Specific <em>KRAS</em> G12C inhibitors have reached the stage of targeted therapy for non-small cell lung cancer (NSCLC). However, there is a dearth of real-world data in the context of immune checkpoint blockade and docetaxel effectiveness in NSCLC patients with <em>KRAS</em> G12C mutations. This study was designed to address this gap in knowledge by analyzing a real-world cohort of patients with <em>KRAS</em> G12C mutations treated with docetaxel in the era of immune-checkpoint-blockade availability.</div></div><div><h3>Patients and Methods</h3><div>The Network Genomic Medicine (NGM) database was queried to identify patients with <em>KRAS</em> G12C mutations who had been treated with docetaxel monotherapy or combinations between July 1st, 2015, and December 31st, 2019.</div></div><div><h3>Results</h3><div>The median rwOS was 7.6 months (95 % CI: 6.5–14.5), with improved outcomes observed for docetaxel plus nintedanib (10.4 months) compared to docetaxel monotherapy (6.5 months). The rwPFS was 3.4 months overall, with combination therapy showing marginally superior efficacy (4.3 vs. 2.2 months). The presence of concomitant mutations in <em>STK11</em> and <em>KEAP1</em> was associated with inferior outcomes, whereas elevated PD-L1 expression was associated with enhanced rwOS. Notably, the inclusion of patients with ECOG 2 or higher underscored the unfavorable outcomes observed in this subgroup, which is typically excluded from pivotal trials.</div></div><div><h3>Conclusion</h3><div>The effectiveness of docetaxel, administered with or without antiangiogenic agents, was found to be limited in a real-world setting of non-small cell lung cancer (NSCLC) patients with a <em>KRAS</em> G12C mutation, emphasizing the need for novel therapies. Comprehensive molecular profiling remains crucial for optimizing treatment outcomes in this heterogeneous subgroup.</div></div>\",\"PeriodicalId\":18129,\"journal\":{\"name\":\"Lung Cancer\",\"volume\":\"209 \",\"pages\":\"Article 108768\"},\"PeriodicalIF\":4.4000,\"publicationDate\":\"2025-09-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Lung Cancer\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0169500225006609\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Lung Cancer","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0169500225006609","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

摘要

背景：特异性KRAS G12C抑制剂已进入非小细胞肺癌（NSCLC）靶向治疗阶段。然而，在KRAS G12C突变的NSCLC患者中，缺乏免疫检查点阻断和多西他赛有效性的真实数据。本研究旨在通过分析在免疫检查点阻断可用性时代接受多西他赛治疗的KRAS G12C突变患者的真实队列来解决这一知识空白。患者和方法：查询网络基因组医学（NGM）数据库，以确定2015年7月1日至2019年12月31日期间接受多西紫杉醇单药或联合治疗的KRAS G12C突变患者。结果：中位rwOS为7.6个月（95% CI: 6.5-14.5），与多西他赛单药治疗（6.5个月）相比，多西他赛联合尼达尼布治疗（10.4个月）的结果有所改善。rwPFS总体为3.4个月，联合治疗的疗效略好（4.3个月对2.2个月）。STK11和KEAP1同时突变的存在与较差的结果相关，而PD-L1表达升高与rwOS增强相关。值得注意的是，纳入ECOG 2或更高的患者强调了在该亚组中观察到的不利结果，该亚组通常被排除在关键试验之外。结论：在KRAS G12C突变的非小细胞肺癌（NSCLC）患者的现实环境中，发现多西他赛联合或不联合抗血管生成药物的有效性有限，强调需要新的治疗方法。全面的分子谱分析对于优化这一异质性亚组的治疗结果仍然至关重要。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

Evaluating docetaxel effectiveness in KRAS G12C-mutated NSCLC: insights from a Real-World cohort

Background

Specific KRAS G12C inhibitors have reached the stage of targeted therapy for non-small cell lung cancer (NSCLC). However, there is a dearth of real-world data in the context of immune checkpoint blockade and docetaxel effectiveness in NSCLC patients with KRAS G12C mutations. This study was designed to address this gap in knowledge by analyzing a real-world cohort of patients with KRAS G12C mutations treated with docetaxel in the era of immune-checkpoint-blockade availability.

Patients and Methods

The Network Genomic Medicine (NGM) database was queried to identify patients with KRAS G12C mutations who had been treated with docetaxel monotherapy or combinations between July 1st, 2015, and December 31st, 2019.

Results

The median rwOS was 7.6 months (95 % CI: 6.5–14.5), with improved outcomes observed for docetaxel plus nintedanib (10.4 months) compared to docetaxel monotherapy (6.5 months). The rwPFS was 3.4 months overall, with combination therapy showing marginally superior efficacy (4.3 vs. 2.2 months). The presence of concomitant mutations in STK11 and KEAP1 was associated with inferior outcomes, whereas elevated PD-L1 expression was associated with enhanced rwOS. Notably, the inclusion of patients with ECOG 2 or higher underscored the unfavorable outcomes observed in this subgroup, which is typically excluded from pivotal trials.

Conclusion

The effectiveness of docetaxel, administered with or without antiangiogenic agents, was found to be limited in a real-world setting of non-small cell lung cancer (NSCLC) patients with a KRAS G12C mutation, emphasizing the need for novel therapies. Comprehensive molecular profiling remains crucial for optimizing treatment outcomes in this heterogeneous subgroup.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Lung Cancer 医学-呼吸系统

CiteScore

9.40

自引率

3.80%

发文量

407

审稿时长

25 days

期刊介绍： Lung Cancer is an international publication covering the clinical, translational and basic science of malignancies of the lung and chest region.Original research articles, early reports, review articles, editorials and correspondence covering the prevention, epidemiology and etiology, basic biology, pathology, clinical assessment, surgery, chemotherapy, radiotherapy, combined treatment modalities, other treatment modalities and outcomes of lung cancer are welcome.