达克替尼作为表皮生长因子受体21L858R突变的晚期非小细胞肺癌患者一线治疗的疗效和安全性：一项中国多中心病例系列研究。
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.
作者信息
Wang Shouzheng, Liu Jiayu, Wang Yan, Hu Ying, Liu Ziling, Yao Yu, Liang Li, Liu Yutao, Wang Lin, Li Junling, Xing Puyuan
机构信息
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/CancerHospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Department of Medical Oncology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China.
出版信息
Chin J Cancer Res. 2024 Aug 30;36(4):398-409. doi: 10.21147/j.issn.1000-9604.2024.04.04.
OBJECTIVE
To provide real-world evidence for the application of first-line dacomitinib treatment for epidermal growth factor receptor () 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 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 . without BM: hazard ratio (HR), 1.331; 95% CI, 0.720-2.458; P=0.361] and initial doses (45 mg 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 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% 7.5%, P=0.042).
CONCLUSIONS
First-line dacomitinib treatment demonstrated promising efficacy and tolerable adverse events among 21L858R mutant NSCLC patients in China.
目的
为一线达可替尼治疗中国表皮生长因子受体（EGFR）21L858R突变的非小细胞肺癌（NSCLC）患者提供真实世界证据，并探索影响疗效和安全性的因素。
方法
开展一项纵向、连续病例系列、多中心研究，数据兼具前瞻性和回顾性。主要终点为无进展生存期（PFS），次要终点包括治疗持续时间（DOT）、总生存期（OS）、客观缓解率（ORR）、疾病控制率（DCR）和安全性。
结果
共纳入155例接受一线达可替尼治疗的EGFR 21L858R突变患者。这些患者的中位随访时间为20.4个月。在134例有可评估病灶的患者中，ORR为70.9%，DCR为96.3%。中位PFS为16.3[95%置信区间（95%CI），13.7 - 18.9]个月。多因素Cox回归分析表明，基线脑转移（BM）状态[有BM与无BM：风险比（HR），1.331；95%CI，0.720 - 2.458；P = 0.361]和初始剂量（45 mg与30 mg：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（95%CI，17.5 - 24.6）个月，中位OS未达到。64例进展后患者进行了基因检测，其中29例（45.3%）患者出现EGFR 20T790M突变。此外，在46例进展后停用达可替尼治疗的患者中，31例（67.4%）患者接受了后续第三代EGFR酪氨酸激酶抑制剂治疗。最常见的3 - 4级不良事件为皮疹（10.4%）、腹泻（9.1%）、口腔炎（7.1%）和甲沟炎（4.5%）。45 mg组3 - 4级皮疹的发生率显著高于30 mg组（21.9%与7.5%，P = 0.042）。
结论
一线达可替尼治疗在中国EGFR 21L858R突变的NSCLC患者中显示出有前景的疗效和可耐受的不良事件。
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