Xie Kang, Wang Jing, Jiang Juan, Deng Zhujun, Hu Qiongxia, Wang Denian
Precision Medicine Centre, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
Oncol Lett. 2025 Apr 28;29(6):316. doi: 10.3892/ol.2025.15062. eCollection 2025 Jun.
Lung cancer remains a leading cause of mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for ~85% of all lung cancer cases. Epidermal growth factor receptor (EGFR) exon 20 insertion mutant NSCLC is rare and associated with poor outcomes. Several novel generations (third-generation) of EGFR-tyrosine kinase inhibitors (TKIs) have been developed for the treatment of NSCLC and have shown antitumour potential. Therefore, the present study reviewed their efficacy and safety outcomes for this condition. A thorough literature searching was performed using the Cochrane Library, Web of Science, PubMed and Embase databases. Clinical trials published in English and reporting overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and treatment relevant adverse events (TRAEs) of grade ≥3 were included for further analysis. A total of 13 studies were included. All included studies reported ORRs with a pooled ORR of 0.486 [95% confidence interval (CI), 0.369-0.602]. Subgroup analysis revealed the following ORRs: 0.731 (95% CI, 0.560-0.901; I=0%) for YK-029A; 0.608 (95% CI, 0.511-0.705; I=0%) for sunvozertinib; 0.602 (95% CI, 0.440-0.764; I=80.2%) for furmonertinib; 0.602 (95% CI, 0.486-0.718; I=84.5%) for befotertinib; 0.566 (95% CI, 0.236-0.896; I=96.3%) for amivantamab; 0.444 (95% CI, 0.215-0.674; I=0%) for BEBT-109; and 0.256 (95% CI, 0.178-0.334; I=75.0%) for poziotinib. The pooled DCR, median PFS and median OS were 0.843 (95% CI, 0.740-0.946), 10.11 months (95% CI, 9.58-10.64 months; I=78.8%; P<0.001) and 23.00 months (95% CI, 20.30-25.69 months; I=44.8; P=0.178), respectively. The pooled incidence of TRAEs of grade ≥3 was 0.458 (95% CI, 0.336-0.580; I=96.9%; P<0.001), with the incidence of the three most reported TRAEs (diarrhoea, thrombocytopenia and anaemia) demonstrated to be 0.112 (95% CI, 0.060-0.164), 0.065 (95% CI, -0.012-0.141) and 0.040 (95% CI, 0.005-0.076), respectively. In conclusion, the emerging EGFR-TKIs for NSCLC with EGFR exon 20 insertion have a promising treatment outcome with a manageable safety profile. However, further analysis is needed when more clinical data are released.
肺癌仍然是全球主要的死亡原因，其中非小细胞肺癌（NSCLC）占所有肺癌病例的约85%。表皮生长因子受体（EGFR）外显子20插入突变的NSCLC较为罕见，且预后较差。已经开发了几代新型（第三代）EGFR酪氨酸激酶抑制剂（TKIs）用于治疗NSCLC，并显示出抗肿瘤潜力。因此，本研究综述了它们在这种情况下的疗效和安全性结果。使用Cochrane图书馆、科学网、PubMed和Embase数据库进行了全面的文献检索。纳入了以英文发表并报告总缓解率（ORR）、疾病控制率（DCR）、无进展生存期（PFS）、总生存期（OS）以及≥3级治疗相关不良事件（TRAEs）的临床试验进行进一步分析。共纳入13项研究。所有纳入研究均报告了ORR，合并ORR为0.486[95%置信区间（CI），0.369 - 0.602]。亚组分析显示以下ORR：YK - 029A为0.731（95%CI，0.560 - 0.901；I = 0%）；sunvozertinib为0.608（95%CI，0.511 - 0.705；I = 0%）；furmonertinib为0.602（95%CI，0.440 - 0.764；I = 80.2%）；befotertinib为0.602（95%CI，0.486 - 0.718；I = 84.5%）；amivantamab为0.566（95%CI，0.236 - 0.896；I = 96.3%）；BEBT - 109为0.444（95%CI，0.215 - 0.674；I = 0%）；poziotinib为0.256（95%CI，0.178 - 0.334；I = 75.0%）。合并DCR、中位PFS和中位OS分别为0.843（95%CI，0.740 - 0.946）、10.11个月（95%CI，9.58 - 10.64个月；I = 78.8%；P < 0.001）和23.00个月（95%CI，20.30 - 25.69个月；I = 44.8；P = 0.178）。≥3级TRAEs的合并发生率为0.458（95%CI，0.336 - 0.580；I = 96.9%；P < 0.001），报告最多的三种TRAEs（腹泻、血小板减少和贫血）的发生率分别为0.112（95%CI，0.060 - 0.164）、0.065（95%CI， - 0.012 - 0.141）和0.040（95%CI，0.005 - 0.076）。总之，用于治疗EGFR外显子20插入的NSCLC的新型EGFR - TKIs具有有前景的治疗结果和可控的安全性。然而，当更多临床数据发布时，还需要进一步分析。
