A pilot study of nintedanib in molecularly selected patients with advanced non-small cell lung cancer.

IF 2.1 3区医学 Q3 RESPIRATORY SYSTEM Journal of thoracic disease Pub Date : 2024-06-30 Epub Date: 2024-06-12 DOI:10.21037/jtd-23-1717

Christine Auberle, Feng Gao, Mark Sloan, Daniel Morgensztern, Linda Winkler, Jeffrey P Ward, Siddhartha Devarakonda, Timothy P Rearden, Ramaswamy Govindan, Saiama N Waqar

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Abstract

Background: Nintedanib is a small molecule tyrosine kinase inhibitor (TKI) targeting vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and fibroblast growth factor receptor (FGFR). The purpose of the study was to evaluate the response rate for patients with advanced non-small cell lung cancer (NSCLC) with mutations in TP53, VEGFR1-3, PDGFR-A, PDGFR-B, and FGFR1-3 treated with nintedanib as part of an open-label, single-arm pilot study.

Methods: Patients with advanced NSCLC previously treated with platinum-doublet chemotherapy with the above mutations were enrolled. Exclusion criteria included necrotic tumors with invasion of blood vessels, history of recent thromboembolic events, increased risk of bleeding or thrombosis, myocardial infarction, and weight loss >10% within past 6 months. Nintedanib was administered at a dose of 200 mg orally twice daily until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Secondary endpoints included progression-free survival (PFS) and correlating outcomes with specific mutations. This study was registered with ClinicalTrials.gov, number NCT02299141.

Results: Between 2015 and 2019, 20 patients were enrolled with a median age was 66 years, 15 (75%) were females, 15 (75%) had adenocarcinoma, and 17 patients had a TP53 mutation (85%). Seventeen (85%) had received prior immunotherapy and 11 (55%) had received at least three prior lines of systemic therapy. The ORR was 15% with three partial responses (PR), while 12 patients had stable disease (SD), with disease control rate (DCR) consisting of a PR and SD greater than or equal to 16 weeks of 65% (n=13). Median PFS was 4.3 months [95% confidence interval (CI): 1.8-7.9] and median overall survival (OS) was 11.3 months (95% CI: 3.5-44.2). Three patients experienced prolonged clinical benefit from nintedanib, remaining on treatment for over 1 year and all three had a TP53 mutation and received prior immunotherapy. The most common adverse events of any grade included nausea (80%), fatigue (70%), diarrhea (60%), and anorexia (60%).

Conclusions: In this pilot study in heavily pretreated and molecularly selected patients with metastatic NSCLC, nintedanib showed modest activity.

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尼替达尼在分子筛选出的晚期非小细胞肺癌患者中的试点研究。

背景：宁替达尼是一种靶向血管内皮生长因子受体（VEGFR）、血小板衍生生长因子受体（PDGFR）和成纤维细胞生长因子受体（FGFR）的小分子酪氨酸激酶抑制剂（TKI）。该研究的目的是评估TP53、VEGFR1-3、PDGFR-A、PDGFR-B和FGFR1-3突变的晚期非小细胞肺癌（NSCLC）患者接受宁替达尼治疗后的应答率，这是一项开放标签、单臂试验研究的一部分：入组患者均为既往接受过铂双联化疗且存在上述突变的晚期 NSCLC 患者。排除标准包括肿瘤坏死并侵犯血管、近期血栓栓塞病史、出血或血栓风险增加、心肌梗死以及过去6个月内体重下降>10%。Nintedanib的口服剂量为200毫克，每天两次，直至疾病进展或出现不可接受的毒性反应。根据实体瘤反应评估标准（RECIST）1.1，主要终点是客观反应率（ORR）。次要终点包括无进展生存期（PFS）以及与特定突变相关的结果。该研究已在ClinicalTrials.gov注册，编号为NCT02299141.Results：2015年至2019年期间，20名患者入组，中位年龄为66岁，15名（75%）为女性，15名（75%）患有腺癌，17名患者有TP53突变（85%）。17名患者（85%）曾接受过免疫疗法，11名患者（55%）曾接受过至少三种系统疗法。ORR为15%，其中有3例部分反应（PR），12例患者病情稳定（SD），疾病控制率（DCR）包括大于或等于16周的PR和SD，为65%（n=13）。中位 PFS 为 4.3 个月[95% 置信区间 (CI)：1.8-7.9]，中位总生存期 (OS) 为 11.3 个月 (95% CI：3.5-44.2)。有3名患者从宁替尼中获得了长期临床获益，治疗时间超过1年，这3名患者都有TP53突变并接受过免疫疗法。最常见的任何级别的不良反应包括恶心（80%）、疲劳（70%）、腹泻（60%）和厌食（60%）：在这项针对重度预处理和分子筛选的转移性 NSCLC 患者的试点研究中，宁替达尼显示出适度的活性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of thoracic disease RESPIRATORY SYSTEM-

CiteScore

4.60

自引率

4.00%

发文量

254

期刊介绍： The Journal of Thoracic Disease (JTD, J Thorac Dis, pISSN: 2072-1439; eISSN: 2077-6624) was founded in Dec 2009, and indexed in PubMed in Dec 2011 and Science Citation Index SCI in Feb 2013. It is published quarterly (Dec 2009- Dec 2011), bimonthly (Jan 2012 - Dec 2013), monthly (Jan. 2014-) and openly distributed worldwide. JTD received its impact factor of 2.365 for the year 2016. JTD publishes manuscripts that describe new findings and provide current, practical information on the diagnosis and treatment of conditions related to thoracic disease. All the submission and reviewing are conducted electronically so that rapid review is assured.