Integrative evaluation of primary and metastatic lesion spectrum to guide anti-PD-L1 therapy of non-small cell lung cancer: results from two randomized studies.
Integrative evaluation of primary and metastatic lesion spectrum to guide anti-PD-L1 therapy of non-small cell lung cancer: results from two randomized studies.
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原发性和转移性病灶谱的综合评估指导非小细胞肺癌的抗 PD-L1 治疗：两项随机研究的结果
DOI：
10.1080/2162402x.2021.1909296
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发表时间：
2021-04-26
期刊：
影响因子：
7.2
通讯作者：
Dong ZY
中科院分区：
文献类型：
--
作者：
Ma SC;Tang XR;Long LL;Bai X;Zhou JG;Duan ZJ;Wang J;Fu QJ;Zhu HB;Guo XJ;Zhang YP;Guo ZQ;Wu DH;Dong ZY
摘要目的：免疫检查点阻断(ICB)与标准化疗在非选择性非小细胞肺癌(NSCLC)中的临床疗效比较。然而，在临床实践中，患者对ICB治疗的反应是不同的。材料和方法：在橡树和杨树试验队列中，我们回顾评估了原发灶和转移灶频谱(基线最长直径之和、转移部位数目和特定器官转移)对阿替唑单抗优于多西紫杉醇疗效的预测作用。开发了一种基于频谱的决策模型DSO(Diameter-Site-Organ)，并验证了该模型对ICB的指导作用。结果：与多西紫杉醇相比，阿替唑单抗具有更高的SLD值(>；38 mm)和更多的转移灶(≥2)，具有显著的总体生存(OS)益处。具体地说，肾上腺和脑转移被认为是阿替唑单抗治疗的有利预测因素。DSO模型是在发现队列中开发的，以整合原发灶和转移灶频谱的指导作用。值得注意的是，随着DSO评分的增加，观察到阿替唑单抗与多西紫杉醇的疗效增强的一般规律。对于DSO评分为0的患者，阿替唑单抗的OS显著长于多西紫杉醇，而在DSO评分≤为0的患者中，两种治疗方法的OS大致相似。同样的发现也出现在内部和外部验证队列中。结论：患者对抗PD-L1治疗的反应因原发灶和转移灶的不同而不同。基于DSO的系统可能为非小细胞肺癌患者的ICB治疗提供有前景的用药指导。
ABSTRACT Objectives: Clinical benefits of immune-checkpoint blockade (ICB) versus standard chemotherapy have been established in unselected non-small cell lung cancer (NSCLC). However, the response to ICB therapy among patients is heterogeneous in clinical practice. Materials and Methods: We retrospectively assessed the predicitive effect of the primary and metastatic lesion spectrum (baseline sum of the longest diameters [SLD], number of metastatic sites and specific organ metastases) on the efficacy of atezolizumab over docetaxel in OAK and POPLAR trial cohorts. A decision model, termed DSO (Diameter-Site-Organ), based on the spectrum was developed and validated for guiding ICB. Results: Higher SLD (>38 mm) and more metastatic sites (≥2) were characterized with pronounced overall survival (OS) benefits from atezolizumab versus docetaxel. Specifically, adrenal gland and brain metastases were identified as favorable predictors of atezolizumab treatment. The DSO model was developed in the discovery cohort to integrate the directive effect of the primary and metastatic lesion spectrum. Remarkably, a general pattern of enhanced efficacy of atezolizumab versus docetaxel was observed along with the increase of the DSO score. For patients with DSO score > 0, atezolizumab yielded a significantly prolonged OS than docetaxel, whereas OS was generally similar between two treatments in patients with DSO score ≤ 0. Equivalent findings were also seen in the internal and external validation cohorts. Conclusions: The response to anti-PD-L1 therapy among patients varied with the primary and metastatic lesion spectrum. The DSO-based system might provide promising medication guidance for ICB treatment in NSCLC patients.