Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan; Cancer Medicine, Cooperative Graduate School, The Jikei University Graduate School of Medicine, Tokyo, Japan.
Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
Lung Cancer. 2024 May;191:107798. doi: 10.1016/j.lungcan.2024.107798. Epub 2024 Apr 23.
In this study, we explored the clinical outcomes of non-small cell lung cancer (NSCLC) patients with EGFR Exon20 in-frame insertions (Exon20ins), and the impact of the location of Exon20ins on these clinical outcomes.
The efficacies of current systemic therapies in NSCLC patients harboring Exon20ins were investigated using a large-scale clinico-genomic database of LC-SCRUM-Asia, and compared with that of amivantamab in the CHRYSALIS trial.
Of the 11,397 patients enrolled in LC-SCRUM-Asia, Exon20ins were detected in 189 patients (1.7 %). Treatment with classical EGFR tyrosine-kinase inhibitors (classical TKIs) was associated with a significantly shorter progression-free survival (PFS) in NSCLC patients with Exon20ins as compared with Exon19 deletions and L858R. Post platinum-based chemotherapy, classical TKIs and immune checkpoint inhibitors (ICIs) were associated with a shorter PFS than with docetaxel in patients with Exon20ins (HR [95 % CI]; TKIs vs docetaxel, 2.16 [1.35-3.46]; ICIs vs docetaxel, 1.49 [1.21-1.84]). Patients treated with amivantamab in the CHRYSALIS trial showed a risk reduction in PFS and overall survival as compared with LC-SCRUM-Asia patients treated with docetaxel, classical TKIs, or ICIs. Among the 189 patients, Exon20ins were classified as near-loop or far-loop insertions in 115 (61 %) and 56 (30 %) patients, respectively. Treatment with osimertinib was associated with a longer PFS in patients with Exon20ins in near-loop as compared with far-loop (median, 5.6 vs. 2.0 months; HR [95 % CI], 0.22 [0.07-0.64]).
After platinum-based chemotherapy, classical TKIs and ICIs are less effective in NSCLC patients with Exon20ins, and amivantamab may be a promising targeted therapy. There is a possibility that the location of Exon20ins has an impact on the efficacy of TKIs.
本研究旨在探讨具有表皮生长因子受体外显子 20 框内插入（Exon20ins）的非小细胞肺癌（NSCLC）患者的临床结局，以及 Exon20ins 位置对这些临床结局的影响。
利用 LC-SCRUM-Asia 的大规模临床基因组数据库，研究 NSCLC 患者中目前系统治疗的疗效，并与 CHRYSALIS 试验中的 amivantamab 进行比较。
在 LC-SCRUM-Asia 纳入的 11397 名患者中，检测到 189 名患者（1.7%）存在 Exon20ins。与 Exon19 缺失和 L858R 相比，接受经典表皮生长因子受体酪氨酸激酶抑制剂（classical TKIs）治疗的 NSCLC 患者的无进展生存期（PFS）明显更短。铂类化疗后，与多西他赛相比，接受 classical TKIs 和免疫检查点抑制剂（ICIs）治疗的患者 PFS 更短（HR [95%CI]；TKIs 对比多西他赛，2.16 [1.35-3.46]；ICIs 对比多西他赛，1.49 [1.21-1.84]）。与 LC-SCRUM-Asia 中接受多西他赛、classical TKIs 或 ICIs 治疗的患者相比，在 CHRYSALIS 试验中接受 amivantamab 治疗的患者的 PFS 和总生存期风险降低。在 189 名患者中，Exon20ins 分别被分类为近环或远环插入，分别有 115 名（61%）和 56 名（30%）患者。与远环相比，接受奥希替尼治疗的 Exon20ins 近环患者的 PFS 更长（中位，5.6 对比 2.0 个月；HR [95%CI]，0.22 [0.07-0.64]）。
铂类化疗后，classical TKIs 和 ICIs 对 Exon20ins 患者的疗效较差，amivantamab 可能是一种有前途的靶向治疗药物。Exon20ins 的位置有可能对 TKI 的疗效产生影响。
