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
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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。
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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.
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