Koyama Nobuyuki, Watanabe Yasutaka, Iwai Yuki, Kawamura Rumi, Miwa Chihiro, Nagai Yoshiaki, Hagiwara Koichi, Koyama Shinichiro
Department of Clinical Oncology, Tokyo Medical University Hachioji Medical Center, Tokyo, Japan.
Chemotherapy. 2017;62(3):151-158. doi: 10.1159/000454944. Epub 2017 Jan 21.
Exon 19 deletion (Del19) and exon 21 L858R substitution (L858R), which account for 90% of epidermal growth factor receptor (EGFR) mutations as common mutations, are associated with favorable outcomes with EGFR-tyrosine kinase inhibitors (TKIs) compared with other uncommon EGFR mutations in non-small-cell lung cancer (NSCLC). However, whether there are differences in overall survival (OS) between patients with these common EGFR mutations remains controversial.
The subjects studied were 74 NSCLC patients with common EGFR mutations treated with gefitinib or erlotinib. Using univariate and multivariate analyses, we retrospectively compared the clinicopahological characteristics of patients harboring Del19 with those harboring L858R.
Compared with patients harboring L858R, EGFR-TKIs provided a significant OS benefit in patients harboring Del19 (p = 0.024), as well as favorable therapeutic responses (p = 0.045) and progression-free survival (PFS) benefits (p = 0.031). In multivariate analyses, Del19 was independently associated with PFS (p = 0.029) and OS (p = 0.009), whereas no parameters other than pleural dissemination at the initial treatment were associated with EGFR mutation types.
Del19 and L858R have distinct prognostic implications and may require individual therapeutic strategies.
外显子19缺失(Del19)和外显子21 L858R替代(L858R)作为常见突变,占表皮生长因子受体(EGFR)突变的90%,与非小细胞肺癌(NSCLC)中其他不常见的EGFR突变相比,EGFR酪氨酸激酶抑制剂(TKIs)治疗可带来更好的预后。然而,这些常见EGFR突变患者的总生存期(OS)是否存在差异仍存在争议。
研究对象为74例接受吉非替尼或厄洛替尼治疗的常见EGFR突变的NSCLC患者。我们采用单因素和多因素分析,回顾性比较了携带Del19的患者与携带L858R的患者的临床病理特征。
与携带L858R的患者相比,EGFR-TKIs在携带Del19的患者中提供了显著的OS获益(p = 0.024),以及良好的治疗反应(p = 0.045)和无进展生存期(PFS)获益(p = 0.031)。在多因素分析中,Del19与PFS(p = 0.029)和OS(p = 0.009)独立相关,而除初始治疗时的胸膜播散外,没有其他参数与EGFR突变类型相关。
Del19和L858R具有不同的预后意义,可能需要个体化的治疗策略。