Altan Mehmet, Sui Dawen, Xu Cai, Simon George R, Sulihem Saliha T, Malveaux Donna, Ponce Darcy, Rinsurongkawong Waree, Rinsurongkawong Vadeerat, Lee J Jack, Zhang Jianjun, Gibbons Don L, Vaporciyan Ara A, Heymach John V, Santorelli Melissa L, Burke Thomas, Williams Loretta A
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
J Immunother Precis Oncol. 2025 Apr 14;8(2):161-171. doi: 10.36401/JIPO-24-26. eCollection 2025 May.
Targeted therapies and immune checkpoint inhibitors (ICIs) have revolutionized the management of metastatic non-small cell lung cancer (NSCLC) over the past decade.
This single-center observational study was conducted to describe programmed death-ligand 1 (PD-L1) testing, choice of therapy, and outcomes for adult patients with stage IV NSCLC initiating first-line therapy from 2017 through 2020, with follow-up through June 2021. Patient characteristics and study assessments were described according to four histomolecular subtypes, defined by histologic characteristics and availability of standard-of-care therapies for molecular subgroups at the time of study conduct.
Of 507 eligible patients with metastatic NSCLC, 85 (17%) had squamous NSCLC; 288 (57%) had nonsquamous NSCLC with no actionable genomic alteration; 44 (9%) had nonsquamous NSCLC with G12C mutation; and 90 (18%) had nonsquamous NSCLC with , V600E, exon 20 insertion, or or genomic alteration. Most tumors were PD-L1 tested. After excluding 40 patients whose PD-L1 testing status was unknown, all but 55 tumors (12%) were tested for PD-L1 expression, and the percentages tested rose from 86% in 2017 to 100% in 2020. From 27% of nonsquamous NSCLC with no actionable genomic alteration to 46% of G12C-mutated NSCLC had PD-L1 expression ≥ 50%. Use of chemotherapy decreased and use of ICI-chemotherapy combinations increased from 2017 to 2020. In the squamous NSCLC group, single or combination chemotherapy was administered most commonly (42%), whereas ICI-chemotherapy combinations were the most common first-line regimens in the three nonsquamous NSCLC histomolecular groups. For patients with NSCLC and no actionable genomic alterations, ICI-chemotherapy combinations were the most common regimens in 2018-2020 in all but the PD-L1 ≥ 50% category, for whom ICI monotherapy was most common every year except 2020. Median overall survival was 25.0 months (95% CI, 19.1-28.3) for all patients, and, by histomolecular cohort, 14.3 months for squamous NSCLC, 25.3 months for nonsquamous NSCLC with no actionable genomic alteration, not reached for G12C-mutated NSCLC, and 27.7 months for nonsquamous NSCLC with other genomic alterations.
Study findings highlight the increased use of PD-L1 testing over the years from 2017 to 2020 and recent changes in therapy, with decreased use of chemotherapy and increased use of ICI-chemotherapy combinations during the study in each histomolecular group. Moreover, we observed improvements in survival for patients with metastatic NSCLC relative to historical real-world data.
在过去十年中,靶向治疗和免疫检查点抑制剂(ICI)彻底改变了转移性非小细胞肺癌(NSCLC)的治疗方式。
本单中心观察性研究旨在描述2017年至2020年开始一线治疗的IV期NSCLC成年患者的程序性死亡配体1(PD-L1)检测、治疗选择和结局,并随访至2021年6月。根据四种组织分子亚型描述患者特征和研究评估,这四种亚型由研究开展时的组织学特征和分子亚组的标准治疗方法的可及性定义。
在507例符合条件的转移性NSCLC患者中,85例(17%)为鳞状NSCLC;288例(57%)为无可操作基因组改变的非鳞状NSCLC;44例(9%)为具有G12C突变的非鳞状NSCLC;90例(18%)为具有V600E、外显子20插入或其他基因组改变的非鳞状NSCLC。大多数肿瘤进行了PD-L1检测。在排除40例PD-L1检测状态未知的患者后,除55个肿瘤(12%)外,所有肿瘤均进行了PD-L1表达检测,检测比例从2017年的86%上升至2020年的100%。无可操作基因组改变的非鳞状NSCLC中PD-L1表达≥50%的比例从27%上升至G12C突变NSCLC的46%。从2017年到2020年,化疗的使用减少,ICI-化疗联合方案的使用增加。在鳞状NSCLC组中,最常给予单药或联合化疗(42%),而ICI-化疗联合方案是三个非鳞状NSCLC组织分子组中最常见的一线治疗方案。对于无可操作基因组改变的NSCLC患者,除PD-L1≥50%类别外,ICI-化疗联合方案是2018 - 2020年最常见的治疗方案,在该类别中,除2020年外每年ICI单药治疗最常见。所有患者的中位总生存期为25.0个月(95%CI,19.1 - 28.3),按组织分子队列划分,鳞状NSCLC为14.3个月,无可操作基因组改变的非鳞状NSCLC为25.3个月,G12C突变NSCLC未达到,具有其他基因组改变的非鳞状NSCLC为27.7个月。
研究结果突出了2017年至2020年期间PD-L1检测的使用增加以及近期治疗的变化,在每个组织分子组的研究期间,化疗使用减少,ICI-化疗联合方案使用增加。此外,相对于历史真实世界数据,我们观察到转移性NSCLC患者的生存有所改善。