PO.CL01.04 · 临床研究
早发低级别不良事件作为晚期NSCLC的预测性生物标志物:一项多治疗队列分析
Early-onset low-grade adverse events as predictive biomarkers in advanced NSCL: A multi-treatment cohort analysis
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
目的:本研究旨在评估早发的1级(G1)和低级别(LG)治疗相关不良事件(TrAE)能否作为不同治疗方式下晚期非小细胞肺癌(NSCLC)良好生存结局的预测标志物。
方法:我们分析了在Moffitt癌症中心接受治疗的11个队列共577例NSCLC患者的数据:5种免疫治疗(n=383)、3种靶向治疗(n=88)和3种化疗(n=106)。分析所用数据包括来自不良事件通用术语标准(CTCAE v4-5)的AE数据、治疗反应(比较缓解者(完全缓解(CR)和部分缓解(PR))与非缓解者(疾病稳定(SD)和疾病进展(PD)),以及使用Wilcoxon两样本检验比较疾病控制(DC:CR/PR/SD)与PD)、采用Kaplan-Meier生存曲线并结合log-rank检验的无进展生存期(PFS)和总生存期(OS)。我们的分析方法利用多个AE参数来构建一套创新的AE生物标志物。早发G1/LG TrAE定义为在治疗开始后30天内发生的事件。
结果:跨所有治疗类型的早发AE分析显示:(a)与化疗和靶向治疗相比,免疫治疗的G1和LG TrAE发生频率更低;(b)在免疫治疗中,较高频率的G1和LG TrAE与更好的治疗反应相关(缓解者对非缓解者p=0.047(G1)和0.069(LG);DC对PD p=0.005(G1)和0.018(LG)),而在化疗和靶向治疗中无显著结果;(c)对于未发生高级别非治疗相关AE(non-TrAE)的患者,若他们频繁经历G1和LG TrAE,其生存结局在免疫治疗中往往优于AE经历较少或没有的患者(中位PFS:5.5对3.5个月,G1 p=0.03;5.5对3.3个月,LG p=0.015;中位OS:18.2对12.2个月,G1 p=0.008;16.1对12.2个月,LG p=0.04)。请注意,non-TrAE是基线健康状况受损的一个强替代指标。若不进行适当校正,该因素可能会混淆所观察到的早发G1和LG TrAE与生存结局之间的关联。在化疗和靶向治疗中,G1和LG TrAE均未显示出显著的生存关联。
结论:治疗开始后30天内发生的G1和LG TrAE与晚期NSCLC更好的治疗反应和改善的生存相关,尤其是在接受免疫治疗的患者中。这些发现支持将早发G1/LG TrAE特征谱用作潜在的预测性生物标志物。
查看英文原文 English abstract
Purpose: This study aims to assess whether early-onset, grade 1 (G1) and low-grade (LG) treatment-related adverse events (TrAEs) can serve as predictive markers for favorable survival outcomes in advanced non-small cell lung cancer (NSCLC) across different treatment modalities.
Methods: We analyzed data from 577 NSCLC patients across 11 cohorts treated at Moffitt Cancer Center: 5 immunotherapies (n=383), 3 targeted therapies (n=88), and 3 chemotherapies (n=106). Data for analysis used AE data derived from Common Terminology Criteria for Adverse Events (CTCAE v4-5), treatment response including comparison of responder (complete response (CR) and partial response (PR)) versus non-responder (stable disease (SD) and progressive disease (PD)) and comparison of disease control (DC: CR/PR/SD) versus PD using Wilcoxon two-sample test, progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier survival curve with log-rank test. Our analytic approach leveraged multiple AE parameters to develop a set of innovative AE biomarkers. Early-onset G1/LG TrAEs were defined as those occurring within 30 days of treatment initiation.
Results: Early-onset AE analysis across all treatment types revealed that (a) Immunotherapy had lower frequency of G1 and LG TrAEs compared to chemotherapy and targeted therapy; (b) higher frequency of G1 and LG TrAEs were associated with better treatment response in immunotherapy (responder vs non-responder with p=0.047 (G1) and 0.069 (LG); DC vs PD with p=0.005 (G1) and 0.018 (LG)), but no significant results in chemotherapy and targeted therapy; (c) For patients who did not encounter HG non-treatment related AEs (non-TrAEs), if they frequently experienced G1 and LG TrAEs, their survival outcomes tended to be better compared to the ones with less or no AE experiences in immunotherapy (median PFS: 5.5 vs 3.5 months with p=0.03 for G1 and 5.5 vs 3.3 months with p=0.015 for LG; median OS: 18.2 vs 12.2 months with p=0.008 for G1 and 16.1 vs 12.2 months with p=0.04 for LG). Please note that non-TrAEs represent a strong surrogate for compromised baseline health status. Without proper adjustment, this factor may confound the observed association between early-onset G1 and LG TrAEs and survival outcomes. For in chemotherapy and targeted therapy, both G1 and LG TrAEs did not show significant survival association.
Conclusion: G1 and LG TrAEs within 30 days of therapy initiation were associated with better treatment response and improved survival in advanced NSCLC, especially in immunotherapy-treated patients. These findings support the use of early-onset G1/LG TrAE profiles as potential predictive biomarkers.
利益披露 Disclosure
D. Chen, None..
Z. Thompson, None..
J. Whiting, None..
S. Viracacha, None.