转移性非小细胞肺癌中免疫检查点抑制剂再激发反应的预测标志物
Predictive markers of response to immune checkpoint inhibitor rechallenge in metastatic non-small cell lung cancer.
作者信息
Musaelyan Aram A, Odintsova Svetlana V, Musaelyan Karina A, Urtenova Magaripa A, Solovyova Ekaterina P, Menshikova Lyubov I, Orlov Sergey V
机构信息
Department of Clinical Oncology, Pavlov First Saint Petersburg State Medical University, 197022 Saint Petersburg, Russia.
EuroCityClinic LLC, 197022 Saint Petersburg, Russia.
出版信息
Explor Target Antitumor Ther. 2024;5(6):1271-1288. doi: 10.37349/etat.2024.00275. Epub 2024 Oct 18.
AIM
The present study aims to evaluate the efficacy of rechallenge with immune checkpoint inhibitors (ICIs) compared to chemotherapy and the predictive role of clinical parameters in non-small cell lung cancer (NSCLC) patients who were rechallenged.
METHODS
The study included 113 metastatic NSCLC patients who had initially responded to ICIs and platinum-based chemotherapy, either in combination in the first line or sequentially in the first and second line, but later experienced disease progression. Of those patients, 52 later received ICI rechallenge and 61 were exposed to chemotherapy.
RESULTS
In the rechallenge cohort, the median age was 67 years, 38 patients were men (73.1%), 26 (50.0%) had squamous cell carcinoma. Patients who underwent ICI rechallenge had longer overall survival (OS) compared to those who received chemotherapy (12.9 months vs. 9.6 months, = 0.008). Multivariate analysis for progression-free survival (PFS) and OS revealed that poor Eastern Cooperative Oncology Group Performance Status (ECOG PS; PFS: = 0.013 and OS: = 0.037), absence of objective response during initial ICI therapy (PFS: = 0.014 and OS: = 0.028), and baseline neutrophil-to-lymphocyte ratio (NLR) ≥ 3.8 (PFS: = 0.001 and OS: = 0.003) were negative predictive factors of ICI rechallenge. The three parameters were included in a risk model named as the NEO score, which stratified patients who received ICI rechallenge into two predictive groups. Patients with ECOG PS 0-1, objective response during initial ICI treatment, and NLR < 3.8 (favorable group) had longer PFS (8.6 months vs. 3.0 months, < 0.001) and OS (16.6 months vs. 5.5 months, < 0.001) compared to those with absence of all three markers (poor group). There was no association between the NEO score and survival outcomes in patients who did not undergo rechallenge.
CONCLUSIONS
ICI rechallenge showed a survival benefit, particularly in NSCLC patients with NLR < 3.8, good ECOG PS, and objective response.
目的
本研究旨在评估与化疗相比，免疫检查点抑制剂（ICI）再挑战的疗效以及临床参数在接受再挑战的非小细胞肺癌（NSCLC）患者中的预测作用。
方法
该研究纳入了113例转移性NSCLC患者，这些患者最初对ICI和铂类化疗有反应，一线联合使用或一线和二线序贯使用，但后来病情进展。其中，52例患者后来接受了ICI再挑战，61例接受了化疗。
结果
在再挑战队列中，中位年龄为67岁，38例为男性（73.1%），26例（50.0%）为鳞状细胞癌。接受ICI再挑战的患者总生存期（OS）长于接受化疗的患者（12.9个月对9.6个月，P = 0.008）。无进展生存期（PFS）和OS的多因素分析显示，东部肿瘤协作组体能状态（ECOG PS）差（PFS：P = 0.013，OS：P = 0.037）、初始ICI治疗期间无客观反应（PFS：P = 0.014，OS：P = 0.028）以及基线中性粒细胞与淋巴细胞比值（NLR）≥3.8（PFS：P = 0.001，OS：P = 0.003）是ICI再挑战的阴性预测因素。这三个参数被纳入一个名为NEO评分的风险模型，该模型将接受ICI再挑战的患者分为两个预测组。与无所有这三个标志物的患者（差组）相比，ECOG PS为0 - 1、初始ICI治疗有客观反应且NLR < 3.8的患者（优组）的PFS更长（8.6个月对3.0个月，P < 0.001），OS也更长（16.6个月对5.5个月，P < 0.001）。未接受再挑战的患者中，NEO评分与生存结局之间无关联。
结论
ICI再挑战显示出生存获益，尤其是在NLR < 3.8、ECOG PS良好且有客观反应的NSCLC患者中。
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