Organ-specific metastatic landscape dissects PD-(L)1 blockade efficacy in advanced non-small cell lung cancer: applicability from clinical trials to real-world practice.
Organ-specific metastatic landscape dissects PD-(L)1 blockade efficacy in advanced non-small cell lung cancer: applicability from clinical trials to real-world practice.
复制标题
DOI：
10.1186/s12916-022-02315-2
复制
发表时间：
2022-04-12
期刊：
影响因子：
9.3
通讯作者：
Dong, Zhong-Yi
中科院分区：
文献类型：
--
作者：
Ma, Si-Cong;Bai, Xue;Guo, Xue-Jun;Liu, Li;Xiao, Lu-Shan;Lin, Yan;Tan, Jia-Le;Cai, Xiao-Ting;Wen, Yu-Xiang;Ma, Hu;Fu, Q. John;Leng, Meng-Xin;Zhang, Yan-Pei;Long, Li-Li;Guo, Ze-Qin;Wu, De-Hua;Zhou, Jian-Guo;Dong, Zhong-Yi
关键词：
由于缺乏对程序性死亡-（配体）1 [PD-(L)1]阻断的预测与预后价值的理解，器官特异性转移背景尚未纳入指导程序性死亡-（配体）1 [PD-(L)1]阻断的临床实践。我们的目标是描述并结合转移器官景观的预测和预后作用来解剖PD-(L)1阻断在非小细胞肺癌（NSCLC）中的疗效。共纳入2062例非小细胞肺癌患者，这些患者来自一项双臂随机试验（OAK）、两项免疫治疗试验（FIR、BIRCH）和一个现实世界队列（NFyy）。根据其治疗依赖的预测意义和治疗独立的预后，将转移器官分为两类。一种基于转移的评分系统（METscore）被开发并验证用于指导PD-(L)1阻断临床试验和现实世界的实践。不同器官特异性转移的患者对免疫治疗的反应存在显著差异，脑和肾上腺转移的患者存活时间较长[总生存期（OS）， p = 0.0105；无进展生存期（PFS）， p = 0.0167]。相比之下，化疗患者的生存结果相似，无论转移部位如何（OS, p = 0.3742； PFS, p = 0.8242）。有趣的是，转移器官景观的免疫治疗预测意义在PD-L1阳性人群（PD-L1 bb0.1 %）中特别提出。其中，在转移到肾上腺、脑和肝脏（第一类器官）中，观察到有利的预测效果与不利的预后效果的矛盾共存，而转移到骨、胸膜、胸腔积液和纵隔（第二类器官）则产生一致的不利的预测和预后效果。METscore能够整合接受PD-(L)1阻断治疗（p < 0.0001）但不接受化疗（p = 0.0805）的非小细胞肺癌患者的整体预后和解剖OS结果的预测和预后效果。同时，METscore的一般性能首先在FIR （p = 0.0350）和BIRCH （p < 0.0001）中得到验证，然后在现实世界的NFyy队列中得到验证（p = 0.0181）。值得注意的是，METscore也适用于临床试验（OS, p = 0.0087； PFS, p = 0.0290）和现实生活（OS, p = 0.0182； PFS, p = 0.0045）中接受PD-(L)1阻断治疗作为一线治疗的患者。器官特异性转移景观可作为免疫治疗的潜在预测因素，METscore可能能够通过基线放射学评估无创伤地预测晚期NSCLC的PD-(L)1阻断疗效。在线版本包含补充材料，可在10.1186/s12916-022-02315-2获得。
Organ-specific metastatic context has not been incorporated into the clinical practice of guiding programmed death-(ligand) 1 [PD-(L)1] blockade, due to a lack of understanding of its predictive versus prognostic value. We aim at delineating and then incorporating both the predictive and prognostic effects of the metastatic-organ landscape to dissect PD-(L)1 blockade efficacy in non-small cell lung cancer (NSCLC). A total of 2062 NSCLC patients from a double-arm randomized trial (OAK), two immunotherapy trials (FIR, BIRCH), and a real-world cohort (NFyy) were included. The metastatic organs were stratified into two categories based on their treatment-dependent predictive significance versus treatment-independent prognosis. A metastasis-based scoring system (METscore) was developed and validated for guiding PD-(L)1 blockade in clinical trials and real-world practice. Patients harboring various organ-specific metastases presented significantly different responses to immunotherapy, and those with brain and adrenal gland metastases survived longer than others [overall survival (OS), p = 0.0105; progression-free survival (PFS), p = 0.0167]. In contrast, survival outcomes were similar in chemotherapy-treated patients regardless of metastatic sites (OS, p = 0.3742; PFS, p = 0.8242). Intriguingly, the immunotherapeutic predictive significance of the metastatic-organ landscape was specifically presented in PD-L1-positive populations (PD-L1 > 1%). Among them, a paradoxical coexistence of a favorable predictive effect coupled with an unfavorable prognostic effect was observed in metastases to adrenal glands, brain, and liver (category I organs), whereas metastases to bone, pleura, pleural effusion, and mediastinum yielded consistent unfavorable predictive and prognostic effects (category II organs). METscore was capable of integrating both predictive and prognostic effects of the entire landscape and dissected OS outcome of NSCLC patients received PD-(L)1 blockade (p < 0.0001) but not chemotherapy (p = 0.0805) in the OAK training cohort. Meanwhile, general performance of METscore was first validated in FIR (p = 0.0350) and BIRCH (p < 0.0001), and then in the real-world NFyy cohort (p = 0.0181). Notably, METscore was also applicable to patients received PD-(L)1 blockade as first-line treatment both in the clinical trials (OS, p = 0.0087; PFS, p = 0.0290) and in the real-world practice (OS, p = 0.0182; PFS, p = 0.0045). Organ-specific metastatic landscape served as a potential predictor of immunotherapy, and METscore might enable noninvasive forecast of PD-(L)1 blockade efficacy using baseline radiologic assessments in advanced NSCLC. The online version contains supplementary material available at 10.1186/s12916-022-02315-2.
登录
查看更多内容
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
影响因子：
7.2
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
通讯作者：
Dong ZY
影响因子：
76.2
作者：
Reck, Martin;Mok, Tony S. K.;Socinski, Mark A.
通讯作者：
Socinski, Mark A.
影响因子：
45.3
作者：
Ballman, Karla V.
通讯作者：
Ballman, Karla V.
DOI：
10.1016/j.jtho.2018.05.004
发表时间：
2018-11
期刊：
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
影响因子：
--
作者：
Spigel DR;Chaft JE;Gettinger S;Chao BH;Dirix L;Schmid P;Chow LQM;Hicks RJ;Leon L;Fredrickson J;Kowanetz M;Sandler A;Funke R;Rizvi NA
通讯作者：
Rizvi NA
影响因子：
64.8
作者：
Mariathasan S;Turley SJ;Nickles D;Castiglioni A;Yuen K;Wang Y;Kadel EE III;Koeppen H;Astarita JL;Cubas R;Jhunjhunwala S;Banchereau R;Yang Y;Guan Y;Chalouni C;Ziai J;Şenbabaoğlu Y;Santoro S;Sheinson D;Hung J;Giltnane JM;Pierce AA;Mesh K;Lianoglou S;Riegler J;Carano RAD;Eriksson P;Höglund M;Somarriba L;Halligan DL;van der Heijden MS;Loriot Y;Rosenberg JE;Fong L;Mellman I;Chen DS;Green M;Derleth C;Fine GD;Hegde PS;Bourgon R;Powles T
通讯作者：
Powles T