Reck Martin, Syrigos Konstantinos, Miliauskas Skaidrius, Van't Westeinde Susan C, Massuti Bartomeu, Buchner Hannes, Salnikov Alexey V, Lorence Robert M, Ellingboe Anne-Marit, Kitzing Thomas, Kerr Keith
Department of Thoracic Oncology, Airway Research Center North (ARCN), German Center of Lung Research (DZL), Lung Clinic, Grosshansdorf, Germany.
National and Kapodistrian University of Athens, Sotiria General Hospital, Athens, Greece.
Transl Lung Cancer Res. 2024 Dec 31;13(12):3364-3381. doi: 10.21037/tlcr-24-326. Epub 2024 Dec 27.
Anti-angiogenic agents, such as nintedanib and ramucirumab, when combined with docetaxel, are subsequent treatment options in patients with non-small cell lung cancer (NSCLC) who have failed on first-line chemotherapy or immunochemotherapy. However, to date, there are no validated predictive biomarkers for efficacy of anti-angiogenic therapies in this setting. The aim of this study was to explore whether genetic or genomic markers, alone or combined with clinical covariates, could be used to predict overall survival (OS) in patients with NSCLC who are eligible for treatment with nintedanib plus docetaxel.
LUME-BioNIS (NCT02671422) was a prospective, non-interventional study that assessed the efficacy and safety of nintedanib plus docetaxel in patients with relapsed/refractory NSCLC. The primary outcome was OS in relation to exploratory molecular biomarkers, alone or in combination with clinical covariates. Exploratory multivariate and univariate analyses were undertaken on putative biomarkers including clinical variables, somatic mutations, gene expression, immunological, and proliferation markers. Sub-analyses in patients with prior immunotherapy were performed.
Of 260 enrolled patients, most patients received nintedanib plus docetaxel in the second-line (68.8%) or third-line (25.8%). After a median follow-up of 19.7 months, median OS was 8.1 months (95% confidence interval: 7.1-9.5). Univariate subgroup analysis indicated that the presence of liver/adrenal metastases, Eastern Cooperative Oncology Group performance status (ECOG PS) ≥1, time since start of first-line therapy (<9 months), and response to first-line therapy had potential prognostic significance for OS. In multivariate analysis, the presence of brain/liver metastases and the presence of >2 metastatic sites at baseline were associated with OS. In univariate analyses in patients with prior immunotherapy, RNA expression levels of genes involved in cell proliferation, DNA damage repair, interferon signaling, and abundance of neutrophils had potential prognostic significance for OS.
Nintedanib plus docetaxel had promising activity and manageable safety in a real-world clinical setting. No new predictive biomarkers were identified to help select patients who may particularly benefit from anti-angiogenic therapy.
抗血管生成药物，如尼达尼布和雷莫西尤单抗，与多西他赛联合使用时，是一线化疗或免疫化疗失败的非小细胞肺癌（NSCLC）患者的后续治疗选择。然而，迄今为止，在这种情况下，尚无经过验证的抗血管生成治疗疗效预测生物标志物。本研究的目的是探讨基因或基因组标志物单独或与临床协变量联合使用是否可用于预测适合接受尼达尼布加量多西他赛治疗的NSCLC患者的总生存期（OS）。
LUME-BioNIS（NCT02671422）是一项前瞻性、非干预性研究，评估了尼达尼布加量多西他赛在复发/难治性NSCLC患者中的疗效和安全性。主要结局是与探索性分子生物标志物单独或与临床协变量联合相关的OS。对包括临床变量、体细胞突变、基因表达、免疫和增殖标志物在内的假定生物标志物进行了探索性多变量和单变量分析。对既往接受过免疫治疗的患者进行了亚组分析。
在260名入组患者中，大多数患者在二线（68.8%）或三线（25.8%）接受了尼达尼布加量多西他赛治疗。中位随访19.7个月后，中位OS为8.1个月（95%置信区间：7.1-9.5）。单变量亚组分析表明，肝/肾上腺转移的存在、东部肿瘤协作组体能状态（ECOG PS）≥1、自一线治疗开始的时间（<9个月）以及对一线治疗的反应对OS具有潜在的预后意义。在多变量分析中，脑/肝转移的存在以及基线时>2个转移部位的存在与OS相关。在既往接受过免疫治疗的患者的单变量分析中，参与细胞增殖、DNA损伤修复、干扰素信号传导的基因的RNA表达水平以及中性粒细胞的丰度对OS具有潜在的预后意义。
在真实世界的临床环境中，尼达尼布加量多西他赛具有良好的活性和可控的安全性。未发现新的预测生物标志物来帮助选择可能特别受益于抗血管生成治疗的患者。
