Efficacy and safety of dacomitinib as first-line treatment for advanced non-small cell lung cancer patients with epidermal growth factor receptor 21L858R mutation: A multicenter, case-series study in China.

IF 7 2区 医学 Q1 ONCOLOGY
Shouzheng Wang, Jiayu Liu, Yan Wang, Ying Hu, Ziling Liu, Yu Yao, Li Liang, Yutao Liu, Lin Wang, Junling Li, Puyuan Xing
{"title":"Efficacy and safety of dacomitinib as first-line treatment for advanced non-small cell lung cancer patients with epidermal growth factor receptor 21L858R mutation: A multicenter, case-series study in China.","authors":"Shouzheng Wang, Jiayu Liu, Yan Wang, Ying Hu, Ziling Liu, Yu Yao, Li Liang, Yutao Liu, Lin Wang, Junling Li, Puyuan Xing","doi":"10.21147/j.issn.1000-9604.2024.04.04","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>To provide real-world evidence for the application of first-line dacomitinib treatment for epidermal growth factor receptor (<i>EGFR</i>) 21L858R mutant non-small cell lung cancer (NSCLC) patients in China and to explore the factors influencing the efficacy and safety.</p><p><strong>Methods: </strong>A longitudinal, consecutive case-series, multicenter study with mixed prospective and retrospective data was conducted. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included duration of treatment (DOT), overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety.</p><p><strong>Results: </strong>A total of 155 <i>EGFR</i> 21L858R mutant patients treated with first-line dacomitinib were included. The median follow-up time for these patients was 20.4 months. Among 134 patients with evaluable lesions, the ORR was 70.9% and the DCR was 96.3%. The median PFS was 16.3 [95% confidence interval (95% CI), 13.7-18.9] months. Multivariate Cox regression analysis suggested that the baseline brain metastasis (BM) status [with <i>vs</i>. without BM: hazard ratio (HR), 1.331; 95% CI, 0.720-2.458; P=0.361] and initial doses (45 mg <i>vs.</i> 30 mg: HR, 0.837; 95% CI, 0.427-1.641; P=0.604) did not significantly affect the median PFS. The median DOT was 21.0 (95% CI, 17.5-24.6) months and the median OS was not reached. Genetic tests were performed in 64 patients after progression, among whom 29 (45.3%) patients developed the <i>EGFR</i> 20T790M mutation. In addition, among the 46 patients who discontinued dacomitinib treatment after progression, 31 (67.4%) patients received subsequent third-generation EGFR-tyrosine kinase inhibitors. The most common grade 3-4 adverse events were rash (10.4%), diarrhea (9.1%), stomatitis (7.1%) and paronychia (4.5%). The incidence of grade 3-4 rash was significantly higher in the 45 mg group than that in the 30 mg group (21.9% <i>vs.</i> 7.5%, P=0.042).</p><p><strong>Conclusions: </strong>First-line dacomitinib treatment demonstrated promising efficacy and tolerable adverse events among <i>EGFR</i> 21L858R mutant NSCLC patients in China.</p>","PeriodicalId":9882,"journal":{"name":"Chinese Journal of Cancer Research","volume":null,"pages":null},"PeriodicalIF":7.0000,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377884/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chinese Journal of Cancer Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21147/j.issn.1000-9604.2024.04.04","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Objective: To provide real-world evidence for the application of first-line dacomitinib treatment for epidermal growth factor receptor (EGFR) 21L858R mutant non-small cell lung cancer (NSCLC) patients in China and to explore the factors influencing the efficacy and safety.

Methods: A longitudinal, consecutive case-series, multicenter study with mixed prospective and retrospective data was conducted. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included duration of treatment (DOT), overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety.

Results: A total of 155 EGFR 21L858R mutant patients treated with first-line dacomitinib were included. The median follow-up time for these patients was 20.4 months. Among 134 patients with evaluable lesions, the ORR was 70.9% and the DCR was 96.3%. The median PFS was 16.3 [95% confidence interval (95% CI), 13.7-18.9] months. Multivariate Cox regression analysis suggested that the baseline brain metastasis (BM) status [with vs. without BM: hazard ratio (HR), 1.331; 95% CI, 0.720-2.458; P=0.361] and initial doses (45 mg vs. 30 mg: HR, 0.837; 95% CI, 0.427-1.641; P=0.604) did not significantly affect the median PFS. The median DOT was 21.0 (95% CI, 17.5-24.6) months and the median OS was not reached. Genetic tests were performed in 64 patients after progression, among whom 29 (45.3%) patients developed the EGFR 20T790M mutation. In addition, among the 46 patients who discontinued dacomitinib treatment after progression, 31 (67.4%) patients received subsequent third-generation EGFR-tyrosine kinase inhibitors. The most common grade 3-4 adverse events were rash (10.4%), diarrhea (9.1%), stomatitis (7.1%) and paronychia (4.5%). The incidence of grade 3-4 rash was significantly higher in the 45 mg group than that in the 30 mg group (21.9% vs. 7.5%, P=0.042).

Conclusions: First-line dacomitinib treatment demonstrated promising efficacy and tolerable adverse events among EGFR 21L858R mutant NSCLC patients in China.

达科米替尼一线治疗表皮生长因子受体21L858R突变的晚期非小细胞肺癌患者的有效性和安全性:中国多中心病例系列研究。
目的为中国表皮生长因子受体(EGFR)21L858R突变非小细胞肺癌(NSCLC)患者应用达科米替尼一线治疗提供实际证据,并探讨影响疗效和安全性的因素:采用前瞻性和回顾性混合数据进行了一项纵向、连续病例系列多中心研究。主要终点为无进展生存期(PFS),次要终点包括疗程(DOT)、总生存期(OS)、客观反应率(ORR)、疾病控制率(DCR)和安全性:共纳入155例接受达科米替尼一线治疗的表皮生长因子受体21L858R突变患者。这些患者的中位随访时间为20.4个月。在134例可评估病灶的患者中,ORR为70.9%,DCR为96.3%。中位 PFS 为 16.3 个月[95% 置信区间(95% CI),13.7-18.9]。多变量考克斯回归分析表明,基线脑转移(BM)状态[有与无BM:危险比(HR),1.331;95% CI,0.720-2.458;P=0.361]和初始剂量(45毫克与30毫克:HR,0.837;95% CI,0.427-1.641;P=0.604)对中位PFS无显著影响。中位 DOT 为 21.0 个月(95% CI,17.5-24.6 个月),未达到中位 OS。64例患者在病情进展后进行了基因检测,其中29例(45.3%)患者出现了表皮生长因子受体20T790M突变。此外,在进展后停止达科米替尼治疗的46名患者中,有31名(67.4%)患者接受了后续的第三代表皮生长因子受体酪氨酸激酶抑制剂治疗。最常见的3-4级不良事件是皮疹(10.4%)、腹泻(9.1%)、口腔炎(7.1%)和脓疱疮(4.5%)。45毫克组的3-4级皮疹发生率明显高于30毫克组(21.9%对7.5%,P=0.042):结论:达科米替尼一线治疗在中国EGFR 21L858R突变NSCLC患者中具有良好的疗效和可耐受的不良反应。
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 求助全文
来源期刊
自引率
9.80%
发文量
1726
审稿时长
4.5 months
期刊介绍: Chinese Journal of Cancer Research (CJCR; Print ISSN: 1000-9604; Online ISSN:1993-0631) is published by AME Publishing Company in association with Chinese Anti-Cancer Association.It was launched in March 1995 as a quarterly publication and is now published bi-monthly since February 2013. CJCR is published bi-monthly in English, and is an international journal devoted to the life sciences and medical sciences. It publishes peer-reviewed original articles of basic investigations and clinical observations, reviews and brief communications providing a forum for the recent experimental and clinical advances in cancer research. This journal is indexed in Science Citation Index Expanded (SCIE), PubMed/PubMed Central (PMC), Scopus, SciSearch, Chemistry Abstracts (CA), the Excerpta Medica/EMBASE, Chinainfo, CNKI, CSCI, etc.
×
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
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
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 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信