PO.CL01.05 · 临床研究
利用全面基因组分析的计算建模预测早期NSCLC的化学免疫治疗获益
Computational modeling of comprehensive genomic profiling to predict chemo-immunotherapy benefit in early stage NSCLC
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：免疫检查点抑制(ICI)单药及与化疗联合(ICI+C)已改变了非小细胞肺癌(NSCLC)的治疗格局。我们此前曾报道过myCare-040研究的结果[1]，在该研究中我们验证了一种算法，能够将ICI+C获益良好的晚期NSCLC患者与无获益者区分开来。为了解该算法所依据的潜在分子机制是否在各疾病分期间保持一致，我们在接受辅助ICI或ICI+C治疗的早期NSCLC患者队列中评估了该算法。
设计：ΔTRI算法利用Cellworks对患者肿瘤基因组学的计算模型，预测与疾病进展相关的生物标志物变化以及ICI+C治疗的潜在获益。此前验证的ΔTRI和临床阈值(16)在51例接受辅助ICI或ICI+C治疗的非鳞状早期NSCLC患者(I期=20，II期=12，IIIA期=19)中进行了评估，这些患者具有完整的临床和基因组信息(Foundation One CDx)，数据来源于全美范围的去标识化ConcertAI Genomics360数据库。
结果：ΔTRI高获益组(ΔTRI≥16，n = 11)的患者在ICI基础上加用化疗后中位OS获得19.4个月的增量获益(logrank p = 0.057，中位OS ICI = 7个月 vs ICI+C = 26.6个月)。相比之下，ΔTRI无获益组(ΔTRI < 16，n = 40)的患者接受ICI+C时OS未见改善(logrank p = 0.84，中位OS ICI = 13个月 vs ICI+C = 9个月)。线性ΔTRI与治疗(ICI vs ICI+C)之间交互作用的似然比检验具有显著性(LR p = 0.038)。针对早期人群的切点优化(ΔTRI = 9)改善了高获益组的logrank统计量(ΔTRI≥9；logrank p = 0.003)。
结论：尽管ΔTRI是在晚期NSCLC患者中开发和验证的，但它在接受辅助ICI或ICI+C治疗的早期NSCLC真实世界患者队列中同样预测了化疗的增量获益。仍需进一步研究以了解如何将这些观察结果转化为临床应用。
1 Aggarawal等，WCLC 2025
查看英文原文 English abstract
Background: Immune checkpoint inhibition (ICI), alone and in combination with chemotherapy (ICI+C), has transformed the treatment landscape for non-small cell lung cancer (NSCLC). We have previously reported results from the myCare-040 study[1], where we validated an algorithm capable of distinguishing advanced NSCLC patients with favorable ICI+C benefit from those with no benefit. To understand whether the underlying molecular mechanisms used by the algorithm are conserved across disease stages, we have evaluated the algorithm in a cohort of patients with early stage NSCLC receiving adjuvant ICI or ICI + C.
Design: The ∆TRI algorithm uses Cellworks' computational model of a patient's tumor genomics to predict biomarker changes related to disease progression and potential benefit from ICI+C therapy. The previously validated ∆TRI and clinical threshold (16) were evaluated in 51 non-squamous, early stage NSCLC patients (Stage I=20, Stage II=12, Stage IIIA=19) receiving adjuvant ICI or ICI+C ,with complete clinical and genomic information (Foundation One CDx) derived from the nationwide (US-based) de-identified ConcertAI Genomics360 database.
Results: Patients in the ∆TRI High Benefit Group (∆TRI ≥ 16, n = 11), had an incremental benefit in median OS of 19.4 months with the addition of chemotherapy to ICI (logrank p = 0.057, median OS ICI = 7 months vs ICI+C = 26.6 months). In contrast, patients in the ∆TRI No Benefit Group (∆TRI < 16, n = 40) showed no improvement in OS when receiving ICI+C (logrank p = 0.84, median OS ICI = 13 months vs ICI+C = 9 months). A likelihood ratio test of interaction between the linear ∆TRI and treatment (ICI versus ICI+C) was significant (LR p = 0.038). Cut-point optimization for the early stage population (∆TRI= 9) improved the logrank statistics in the High Benefit Group (∆TRI ≥ 9; logrank p = 0.003).
Conclusions: Although developed and validated in patients with advanced NSCLC, the ∆TRI also predicted incremental chemotherapy benefit in an real-world cohort of patients with early stage NSCLC receiving adjuvant ICI or ICI+C. Further work is needed to understand how these observations could be translated into clinical use.
1 Aggarawal et al, WCLC 2025
利益披露 Disclosure
P. Nair,
Cellworks Employment.
K. Promod,
Cellworks Employment.
A. Kumar,
Cellworks Employment.
S. Khandelwal,
Cellworks Employment.
A. Ambreen,
Cellworks Employment.
S. George,
Cellworks Employment.
M. Patil,
Cellworks Employment.
D. Lala,
Cellworks Employment.
A. Bala,
Cellworks Employment.
V. Balakrishnan,
Cellworks Employment.
S. Kapoor,
Cellworks Employment.
D. Watson,
Cellworks Independent Contractor, Stock.
J. Wingrove,
Cellworks Employment, Stock Option.