Department of Internal Medicine, National Taiwan University Cancer Center, National Taiwan University, Taipei, Taiwan.
Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan.
Int J Cancer. 2023 Jul 15;153(2):352-363. doi: 10.1002/ijc.34507. Epub 2023 Mar 21.
EGFR exon 19 deletion (Del-19) comprises multiple advanced NSCLC subtypes. EGFR-tyrosine kinase inhibitor (TKI) efficacy and T790M acquisition in various Del-19 subtypes is unknown. We prospectively collected tissue samples from patients harboring NSCLC with Del-19 between 2006 and 2020. We evaluated EGFR-TKI treatment effectiveness among the different Del-19 subtypes. We collected 1391 NSCLC samples from 892 patients with Del-19, and the most common subtype was del E746-A750 (67.5%). 741 patients had taken first- or second-generation EGFR-TKIs. There were no significant differences in response rates between patients with different Del-19 subtypes (P = .630). Patients with indel E746 had the longest median PFS (14.6 months), but those with non-LRE deletions had the shortest PFS (8.9 months; P = .002). For OS analysis, patients with indel E746 also had the longest OS (34.1 months), but those with non-LRE deletions had the shortest OS (21.1 months; P = .046). Patients with different Del-19 subtypes showed no significant differences in the T790M acquisition rates (P = .443). Among the 151 patients with acquired T790M who received third-generation EGFR-TKIs, the Del-19 subtype was not associated with different RR and PFS. In vitro cellular viability and activation of the EGFR pathway analysis were consistent with the clinical findings. In conclusion, compared with del E746-A750, indel E746 was associated with longer PFS and OS, but the non-LRE subtype was correlated with shorter survival prognosis. There were no significant differences in the acquired T790M rate and treatment effectiveness of subsequent third-generation EGFR-TKIs between various Del-19 subgroups.
EGFR 外显子 19 缺失（Del-19）包含多种晚期 NSCLC 亚型。不同 Del-19 亚型的 EGFR 酪氨酸激酶抑制剂（TKI）疗效和 T790M 获得情况尚不清楚。我们前瞻性地收集了 2006 年至 2020 年间患有 Del-19 的 NSCLC 患者的组织样本。我们评估了不同 Del-19 亚型中 EGFR-TKI 治疗的有效性。我们从 892 名患有 Del-19 的 NSCLC 患者中收集了 1391 个 NSCLC 样本，最常见的亚型是 del E746-A750（67.5%）。741 名患者接受了第一代或第二代 EGFR-TKI 治疗。不同 Del-19 亚型的患者的缓解率没有显著差异（P=0.630）。具有 indel E746 的患者的中位 PFS 最长（14.6 个月），但具有非 LRE 缺失的患者的 PFS 最短（8.9 个月；P=0.002）。对于 OS 分析，具有 indel E746 的患者的 OS 也最长（34.1 个月），但具有非 LRE 缺失的患者的 OS 最短（21.1 个月；P=0.046）。不同 Del-19 亚型的患者在 T790M 获得率方面没有显著差异（P=0.443）。在接受第三代 EGFR-TKI 治疗的 151 名获得 T790M 的患者中，Del-19 亚型与不同的 RR 和 PFS 无关。体外细胞活力和 EGFR 通路激活分析与临床发现一致。总之，与 del E746-A750 相比，indel E746 与更长的 PFS 和 OS 相关，但非 LRE 亚型与更短的生存预后相关。不同的 Del-19 亚组之间在获得 T790M 的比率和随后第三代 EGFR-TKI 的治疗效果方面没有显著差异。
