Analysis of Baseline Molecular Factors Associated With the Risk of Central Nervous System Progression Among Alectinib-Treated Patients With ALK–Positive NSCLC

Lianxi Song MD , Huan Yan MD , Qinqin Xu MD , Chunhua Zhou MD , Juan Liang MD , Shaoding Lin MD , Ruiguang Zhang MD , Juan Yu MD , Yang Xia MD , Nong Yang MD , Liang Zeng MD , Yongchang Zhang MD
{"title":"Analysis of Baseline Molecular Factors Associated With the Risk of Central Nervous System Progression Among Alectinib-Treated Patients With ALK–Positive NSCLC","authors":"Lianxi Song MD ,&nbsp;Huan Yan MD ,&nbsp;Qinqin Xu MD ,&nbsp;Chunhua Zhou MD ,&nbsp;Juan Liang MD ,&nbsp;Shaoding Lin MD ,&nbsp;Ruiguang Zhang MD ,&nbsp;Juan Yu MD ,&nbsp;Yang Xia MD ,&nbsp;Nong Yang MD ,&nbsp;Liang Zeng MD ,&nbsp;Yongchang Zhang MD","doi":"10.1016/j.jtocrr.2024.100729","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><div>Despite receiving alectinib therapy, patients with ALK-positive NSCLC remain at risk of central nervous system (CNS) progression. Our retrospective study aimed to identify baseline clinical and molecular factors associated with the risk of CNS progression in this patient subset.</div></div><div><h3>Methods</h3><div>We analyzed the clinical, molecular, and imaging data of 318 patients with ALK-positive advanced NSCLC who received alectinib as first-line (1L-alectinib) or second-line (2L-alectinib) therapy at baseline (1L, n = 183; 2L, n = 135) and at disease progression (1L, n = 80; 2L, n = 76).</div></div><div><h3>Results</h3><div>The incidence rates of CNS progression were 23.7% after 1L-alectinib treatment and 31.6% after 2L-alectinib treatment. Compared with patients who received 1L-alectinib, CNS progression was similar in patients who received 2L-alectinib (<em>p</em> &gt; 0.05). Oligoprogression was detected in 55.0% (44 of 80) of patients who progressed after first-line alectinib, with the remaining 45.0% (36 of 80) having nonoligoprogression. Univariate and multivariate analyses and stepwise regression analyses consistently identified a higher likelihood of CNS progression among (1) patients who received 2L-alectinib than 1L-alectinib, (2) patients with non-3a/b variant <em>ALK</em> fusion than those with echinoderm microtubule-associated protein-like 4<em>–ALK</em> variant 3a/b, and (3) patients with programmed death ligand 1 (PD-L1) tumor proportion score (TPS) of 50% or higher than PD-L1 TPS of less than 50%.</div></div><div><h3>Conclusions</h3><div>Our study provided real-world evidence that patients who harbored PD-L1 TPS of 50% or higher were more likely to experience CNS progression during alectinib therapy. The association between CNS progression and breakpoint variants warrants further investigation. Our findings suggest that close monitoring and prompt intervention are crucial in prolonging the quality of life of this patient subset.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 12","pages":"Article 100729"},"PeriodicalIF":3.0000,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"JTO Clinical and Research Reports","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2666364324000997","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Introduction

Despite receiving alectinib therapy, patients with ALK-positive NSCLC remain at risk of central nervous system (CNS) progression. Our retrospective study aimed to identify baseline clinical and molecular factors associated with the risk of CNS progression in this patient subset.

Methods

We analyzed the clinical, molecular, and imaging data of 318 patients with ALK-positive advanced NSCLC who received alectinib as first-line (1L-alectinib) or second-line (2L-alectinib) therapy at baseline (1L, n = 183; 2L, n = 135) and at disease progression (1L, n = 80; 2L, n = 76).

Results

The incidence rates of CNS progression were 23.7% after 1L-alectinib treatment and 31.6% after 2L-alectinib treatment. Compared with patients who received 1L-alectinib, CNS progression was similar in patients who received 2L-alectinib (p > 0.05). Oligoprogression was detected in 55.0% (44 of 80) of patients who progressed after first-line alectinib, with the remaining 45.0% (36 of 80) having nonoligoprogression. Univariate and multivariate analyses and stepwise regression analyses consistently identified a higher likelihood of CNS progression among (1) patients who received 2L-alectinib than 1L-alectinib, (2) patients with non-3a/b variant ALK fusion than those with echinoderm microtubule-associated protein-like 4–ALK variant 3a/b, and (3) patients with programmed death ligand 1 (PD-L1) tumor proportion score (TPS) of 50% or higher than PD-L1 TPS of less than 50%.

Conclusions

Our study provided real-world evidence that patients who harbored PD-L1 TPS of 50% or higher were more likely to experience CNS progression during alectinib therapy. The association between CNS progression and breakpoint variants warrants further investigation. Our findings suggest that close monitoring and prompt intervention are crucial in prolonging the quality of life of this patient subset.
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
与阿来替尼治疗的ALK阳性NSCLC患者中枢神经系统进展风险相关的基线分子因素分析
简介尽管接受了阿来替尼治疗,ALK 阳性 NSCLC 患者仍有中枢神经系统(CNS)恶化的风险。我们的回顾性研究旨在确定与该患者亚群中枢神经系统进展风险相关的基线临床和分子因素。方法我们分析了318例ALK阳性晚期NSCLC患者的临床、分子和影像学数据,这些患者在基线时(1L,n = 183;2L,n = 135)和疾病进展时(1L,n = 80;2L,n = 76)接受了阿来替尼一线(1L-alectinib)或二线(2L-alectinib)治疗。结果1L-alectinib治疗后中枢神经系统进展发生率为23.7%,2L-alectinib治疗后为31.6%。与接受1L-阿来替尼治疗的患者相比,接受2L-阿来替尼治疗的患者中枢神经系统进展情况相似(p > 0.05)。在一线阿来替尼治疗后出现进展的患者中,55.0%(80 人中有 44 人)发现了寡进展,其余 45.0%(80 人中有 36 人)为非寡进展。单变量和多变量分析以及逐步回归分析一致发现,在以下患者中,中枢神经系统进展的可能性更高:(1)接受 2L-alectinib 治疗的患者比接受 1L-alectinib 治疗的患者、(2) 非3a/b变异型ALK融合患者比棘皮微管相关蛋白样4-ALK变异型3a/b患者;以及 (3) 程序性死亡配体1(PD-L1)肿瘤比例评分(TPS)达到或超过50%的患者比PD-L1 TPS低于50%的患者。结论我们的研究提供了真实世界的证据,表明PD-L1 TPS为50%或更高的患者在阿来替尼治疗期间更有可能出现中枢神经系统进展。中枢神经系统进展与断点变异之间的关联值得进一步研究。我们的研究结果表明,密切监测和及时干预对于延长这一患者亚群的生活质量至关重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
CiteScore
4.20
自引率
0.00%
发文量
145
审稿时长
19 weeks
期刊最新文献
First Report of Response to Tarlatamab in a Patient With DLL3-Positive Pulmonary Carcinoid: Case Report A Response to the Letter to the Editor: “Heart and Lung Dose as Predictors of Overall Survival in Patients With Locally Advanced Lung Cancer: A National Multicenter Study” Racial Differences in Systemic Immune Parameters in Individuals With Lung Cancer Brief Report of a New Anatomical Region at Risk in Thoracic Radiotherapy: From Discovery to Implementation Entrectinib-Induced Myocarditis and Acute Heart Failure Responding to Steroid Treatment: A Case Report
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1