Efficacy and safety of utidelone for the treatment of patients with locally advanced or metastatic non-small-cell lung cancer who have failed standard second-line treatment: A phase 2 clinical trial (BG01-1801)

Yuankai Shi , Gongyan Chen , Yanqiu Zhao , Jing Zhao , Lin Lin
{"title":"Efficacy and safety of utidelone for the treatment of patients with locally advanced or metastatic non-small-cell lung cancer who have failed standard second-line treatment: A phase 2 clinical trial (BG01-1801)","authors":"Yuankai Shi ,&nbsp;Gongyan Chen ,&nbsp;Yanqiu Zhao ,&nbsp;Jing Zhao ,&nbsp;Lin Lin","doi":"10.1016/j.cpt.2023.10.006","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Chemotherapy remains the standard-of-care for many patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC), but acquired resistance presents challenges. The aim of this open-label, multicenter phase 2 clinical trial was to determine the efficacy and safety of utidelone, a novel genetically engineered epothilone analog and microtubule-stabilizing agent, as a third- or later-line treatment for locally advanced or metastatic NSCLC.</p></div><div><h3>Methods</h3><p>Patients who had failed standard second-line treatment (including platinum-containing chemotherapy or targeted therapy) received utidelone (40 mg/m<sup>2</sup> via intravenous injection daily, day 1–5) every 21 days. The primary endpoint was the objective response rate (ORR). Secondary endpoints were the duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety.</p></div><div><h3>Results</h3><p>From March 12, 2019 to January 18, 2021, 26 pretreated patients with locally advanced or metastatic NSCLC (100% of patients had received prior platinum and 65.4% patients had received prior taxane treatment) were enrolled (80.8% of patients had adenocarcinoma). At baseline, nine (34.6%) patients had received second-line treatment, 10 (38.5%) patients had received third-line treatment, and seven (26.9%) patients had received fourth- or later-line treatment. By the data cut-off date of August 10, 2021, the median follow-up was 7.49 months (range, 1.4–26.7 months). The ORR was 15.4% (95% confidence interval [CI], 4.4%–34.9%) in the intention-to-treat (ITT) cohort (<em>N</em> = 26) and 19.0% (95% CI, 5.4%–41.9%) in the per-protocol (PP) cohort (<em>N</em> = 21). The disease control rate was 69.2% (95% CI, 48.2%–85.7%) and 81.0% (95% CI, 58.1%–94.6%) in the ITT and PP cohorts, respectively. The median DoR was 4.1 months (95% CI, 3.1–5.1 months) in the ITT cohort. The median PFS was 4.37 months (95% CI, 2.50–5.29 months) in the ITT cohort and 4.37 months (95% CI, 2.50–9.76 months) in the PP cohort. The median OS was not reached, and the 12-month OS rate was 69% (95% CI, 45.1%–84.1%). Grade 3/4 treatment-emergent adverse events occurred in 38.5% of patients, and the most common was peripheral neuropathy (23.1%, all Grade 3), which was manageable with dose modifications.</p></div><div><h3>Conclusions</h3><p>In this clinical trial, utidelone showed promising efficacy and had a manageable safety profile. Further clinical studies are warranted to confirm its role in NSCLC treatment.</p></div><div><h3>Trial registration</h3><p>No.NCT03693547; <span>https://classic.clinicaltrials.gov</span><svg><path></path></svg>.</p></div>","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"2 2","pages":"Pages 103-111"},"PeriodicalIF":0.0000,"publicationDate":"2023-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949713223000885/pdfft?md5=4f7f4f771b7361e58a706b4ed2e5e404&pid=1-s2.0-S2949713223000885-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer pathogenesis and therapy","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2949713223000885","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

Abstract

Background

Chemotherapy remains the standard-of-care for many patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC), but acquired resistance presents challenges. The aim of this open-label, multicenter phase 2 clinical trial was to determine the efficacy and safety of utidelone, a novel genetically engineered epothilone analog and microtubule-stabilizing agent, as a third- or later-line treatment for locally advanced or metastatic NSCLC.

Methods

Patients who had failed standard second-line treatment (including platinum-containing chemotherapy or targeted therapy) received utidelone (40 mg/m2 via intravenous injection daily, day 1–5) every 21 days. The primary endpoint was the objective response rate (ORR). Secondary endpoints were the duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety.

Results

From March 12, 2019 to January 18, 2021, 26 pretreated patients with locally advanced or metastatic NSCLC (100% of patients had received prior platinum and 65.4% patients had received prior taxane treatment) were enrolled (80.8% of patients had adenocarcinoma). At baseline, nine (34.6%) patients had received second-line treatment, 10 (38.5%) patients had received third-line treatment, and seven (26.9%) patients had received fourth- or later-line treatment. By the data cut-off date of August 10, 2021, the median follow-up was 7.49 months (range, 1.4–26.7 months). The ORR was 15.4% (95% confidence interval [CI], 4.4%–34.9%) in the intention-to-treat (ITT) cohort (N = 26) and 19.0% (95% CI, 5.4%–41.9%) in the per-protocol (PP) cohort (N = 21). The disease control rate was 69.2% (95% CI, 48.2%–85.7%) and 81.0% (95% CI, 58.1%–94.6%) in the ITT and PP cohorts, respectively. The median DoR was 4.1 months (95% CI, 3.1–5.1 months) in the ITT cohort. The median PFS was 4.37 months (95% CI, 2.50–5.29 months) in the ITT cohort and 4.37 months (95% CI, 2.50–9.76 months) in the PP cohort. The median OS was not reached, and the 12-month OS rate was 69% (95% CI, 45.1%–84.1%). Grade 3/4 treatment-emergent adverse events occurred in 38.5% of patients, and the most common was peripheral neuropathy (23.1%, all Grade 3), which was manageable with dose modifications.

Conclusions

In this clinical trial, utidelone showed promising efficacy and had a manageable safety profile. Further clinical studies are warranted to confirm its role in NSCLC treatment.

Trial registration

No.NCT03693547; https://classic.clinicaltrials.gov.

Abstract Image

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
优替龙治疗标准二线治疗失败的局部晚期或转移性非小细胞肺癌患者的疗效和安全性:2期临床试验(BG01-1801)
背景化疗仍然是许多局部晚期或转移性非小细胞肺癌(NSCLC)患者的标准治疗方法,但获得性耐药性带来了挑战。这项开放标签、多中心2期临床试验的目的是确定乌地龙(一种新型基因工程埃博霉素类似物和微管稳定剂)作为局部晚期或转移性NSCLC三线或二线治疗的疗效和安全性。主要终点是客观反应率(ORR)。次要终点为反应持续时间(DoR)、无进展生存期(PFS)、总生存期(OS)和安全性。结果从2019年3月12日至2021年1月18日,26名接受过预处理的局部晚期或转移性NSCLC患者(100%的患者既往接受过铂类治疗,65.4%的患者既往接受过类固醇治疗)入组(80.8%的患者为腺癌)。基线时,9 名患者(34.6%)接受过二线治疗,10 名患者(38.5%)接受过三线治疗,7 名患者(26.9%)接受过四线或四线以上治疗。数据截止日期为 2021 年 8 月 10 日,中位随访时间为 7.49 个月(1.4-26.7 个月)。意向治疗(ITT)队列(26 人)的 ORR 为 15.4%(95% 置信区间 [CI],4.4%-34.9%),按方案(PP)队列(21 人)的 ORR 为 19.0%(95% 置信区间 [CI],5.4%-41.9%)。ITT队列和PP队列的疾病控制率分别为69.2%(95% CI,48.2%-85.7%)和81.0%(95% CI,58.1%-94.6%)。ITT队列的中位DoR为4.1个月(95% CI,3.1-5.1个月)。ITT队列的中位PFS为4.37个月(95% CI,2.50-5.29个月),PP队列的中位PFS为4.37个月(95% CI,2.50-9.76个月)。未达到中位OS,12个月OS率为69%(95% CI,45.1%-84.1%)。38.5%的患者发生了3/4级治疗突发不良事件,最常见的是周围神经病变(23.1%,均为3级),通过调整剂量可以控制。试验注册号:NCT03693547;https://classic.clinicaltrials.gov。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Cancer pathogenesis and therapy
Cancer pathogenesis and therapy Surgery, Radiology and Imaging, Cancer Research, Oncology
CiteScore
0.80
自引率
0.00%
发文量
0
审稿时长
54 days
期刊最新文献
Table of Contents Breast cancer risk associated with BRCA1 and BRCA2 pathogenic variants in the Eastern Chinese population Factors affecting the place of death in patients with liver cancer in China, 2013–2020: A population-based study Cardiotoxicity in platinum-based chemotherapy: Mechanisms, manifestations, and management Exploring the significance of extracellular vesicles: Key players in advancing cancer and possible theranostic tools
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1