目前缺乏针对携带HER2突变的非小细胞肺癌(NSCLC)患者的有效治疗。我们检查的有效性和安全性,和潜在的抵抗机制,pyrotinib,泛HER抑制剂,在携带HER2突变的晚期NSCLC中。
在这个多中心,单臂,第二阶段试验,携带HER2突变的IIIB-IV期NSCLC患者,如使用下一代测序确定的,入选并接受400mg/天剂量的吡唑替尼治疗。主要终点是6个月无进展生存率(PFS),次要终点是客观反应率(ORR),PFS,总生存期(OS),疾病控制率(DCR),和安全。还探讨了不同HER2突变类型对吡罗替尼敏感性的影响以及利用源自循环肿瘤DNA(ctDNA)的突变谱预测疾病进展的潜力。
对78例患者进行疗效和安全性分析。6个月PFS率为49.5%(95%置信区间[CI],39.2-60.8)。Pyrotinib产生的ORR为19.2%(95%CI,11.2-30.0),中位PFS为5.6个月(95%CI,2.8-8.4),中位OS为10.5个月(95%CI,8.7-12.3)。中位缓解时间为9.9个月(95%CI,6.2-13.6)。所有治疗相关不良事件(TRAEs)均为1-3级(所有,91.0%;三级,20.5%),最常见的TRAE是腹泻(所有,85.9%;三级、16.7%)。具有外显子20和非外显子20HER2突变的患者的ORR分别为17.7%和25.0%,分别。基线和先前接触阿法替尼的脑转移与ORR无关,PFS,或操作系统。在疾病进展时检测到HER2和EGFR中HER2突变的缺失和扩增的出现。
Pyrotinib在携带外显子20和非外显子20HER2突变的NSCLC患者中表现出良好的疗效和可接受的安全性,值得进一步研究。
中国临床试验注册标识符:ChiCTR1800020262。
There is currently a lack of effective treatments for non-small cell lung cancer (NSCLC) patients harboring HER2 mutations. We examined the efficacy and safety of, and potential resistance mechanism to, pyrotinib, a pan-HER inhibitor, in advanced NSCLC carrying HER2 mutations.
In this multicenter, single-arm, phase II
trial, stage IIIB-IV NSCLC patients harboring HER2 mutations, as determined using next-generation sequencing, were enrolled and treated with pyrotinib at a dose of 400 mg/day. The primary endpoint was 6-month progression-free survival (PFS) rate, and secondary endpoints were objective response rate (ORR), PFS, overall survival (OS), disease control rate (DCR), and safety. The impact of different HER2 mutation types on sensitivity to pyrotinib and the potential of utilizing mutational profile derived from circulating tumor DNA (ctDNA) to predict disease progression were also explored.
Seventy-eight patients were enrolled for efficacy and safety analysis. The 6-month PFS rate was 49.5% (95% confidence interval [CI], 39.2-60.8). Pyrotinib produced an ORR of 19.2% (95% CI, 11.2-30.0), with median PFS of 5.6 months (95% CI, 2.8-8.4), and median OS of 10.5 months (95% CI, 8.7-12.3). The median duration of response was 9.9 months (95% CI, 6.2-13.6). All treatment-related adverse events (TRAEs) were grade 1-3 (all, 91.0%; grade 3, 20.5%), and the most common TRAE was diarrhea (all, 85.9%; grade 3, 16.7%). Patients with exon 20 and non-exon 20 HER2 mutations had ORRs of 17.7% and 25.0%, respectively. Brain metastases at baseline and prior exposure to afatinib were not associated with ORR, PFS, or OS. Loss of HER2 mutations and appearance of amplification in HER2 and EGFR were detected upon disease progression.
Pyrotinib exhibited promising efficacy and acceptable safety in NSCLC patients carrying exon 20 and non-exon 20 HER2 mutations and is worth further investigation.
Chinese Clinical
Trial Registry Identifier: ChiCTR1800020262.