Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.
Medicine (Baltimore). 2022 Nov 4;101(44):e31337. doi: 10.1097/MD.0000000000031337.
Non-small-cell lung cancer (NSCLC) harboring human epidermal growth factor receptor 2 (HER2) exon 20 mutant occurs in 3% of NSCLCs. Targeted agents for this population remain an unmet need. In this analysis, we pooled-analyzed the efficacy and safety of poziotinib, a novel tyrosine kinase inhibitor, in HER2 exon 20 mutant NSCLC.
PubMed, Embase, Web of Science, and Cochrane CENTRAL databases were systematically searched on March 9, 2022. The primary endpoints were objective response rate (ORR) and disease control rate. The secondary endpoint was treatment-related adverse events.
Three prospective clinical trials, involving 126 patients, were identified. The pooled ORR and disease control rate of poziotinib in HER2 exon 20 mutant NSCLC were 27% (95% CI, 19-35) and 72% (95% CI, 64-80), respectively. Patients with G778_P780dupGSP had the highest ORR (88%; 95% CI, 33-100; n = 12), followed by Y772_A775dupYVMA (20%; 95% CI, 12-30; n = 88) and G776delinsVC (19%; 95% CI, 0-50; n = 13). The most common grade 3 to 4 treatment-related adverse events were skin rash (36%), diarrhea (23%), and oral mucositis (13%).
Poziotinib demonstrates moderate antitumor activity in previously treated HER2 exon 20 mutant NSCLC patients with a manageable safety profile. In addition, different subgroup mutations show various benefits of poziotinib treatment. Large-scale and multiarm clinical trials are warranted to confirm a suitable population and therapeutic strategies.
非小细胞肺癌（NSCLC）中存在人类表皮生长因子受体 2（HER2）外显子 20 突变的情况占 NSCLC 的 3%。针对这一人群的靶向药物仍然存在未满足的需求。在这项分析中，我们对新型酪氨酸激酶抑制剂波齐替尼治疗 HER2 外显子 20 突变 NSCLC 的疗效和安全性进行了汇总分析。
于 2022 年 3 月 9 日系统地检索了 PubMed、Embase、Web of Science 和 Cochrane CENTRAL 数据库。主要终点为客观缓解率（ORR）和疾病控制率。次要终点为与治疗相关的不良事件。
确定了三项涉及 126 名患者的前瞻性临床试验。波齐替尼治疗 HER2 外显子 20 突变 NSCLC 的汇总 ORR 和疾病控制率分别为 27%（95%CI，19-35）和 72%（95%CI，64-80）。G778_P780dupGSP 突变患者的 ORR 最高（88%；95%CI，33-100；n=12），其次是 Y772_A775dupYVMA（20%；95%CI，12-30；n=88）和 G776delinsVC（19%；95%CI，0-50；n=13）。最常见的 3 级至 4 级与治疗相关的不良事件是皮疹（36%）、腹泻（23%）和口腔黏膜炎（13%）。
波齐替尼在先前治疗过的 HER2 外显子 20 突变 NSCLC 患者中表现出中等抗肿瘤活性，且安全性可管理。此外，不同亚组突变显示出波齐替尼治疗的不同获益。需要进行大规模、多臂临床试验来证实合适的人群和治疗策略。
