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

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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.
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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。
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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
Radiotherapy Improves Survival in NSCLC After Oligoprogression on Immunotherapy: A Cohort Study Analysis of Baseline Molecular Factors Associated With the Risk of Central Nervous System Progression Among Alectinib-Treated Patients With ALK–Positive NSCLC Regarding: “Olloni A, et al. Heart and Lung Dose as Predictors of Overall Survival in Patients With Locally Advanced Lung Cancer. A National Multicenter Study” Synchronous Oligometastasis and Oligoprogression as a Prognostic Marker in Patients With Extensive-Stage SCLC Treated With a Combination of Immune-Checkpoint Inhibitor and Chemotherapy (HOT2301) The Whole Picture of First-Line Osimertinib for EGFR Mutation-Positive Advanced NSCLC: Real-World Efficacy, Safety, Progression Pattern, and Posttreatment Therapy (Reiwa Study)
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