Department of Thoracic Oncology, Aichi Cancer Center Hospital, Aichi, Japan.
Department of Thoracic Oncology, Aichi Cancer Center Hospital, Aichi, Japan.
Clin Lung Cancer. 2017 Nov;18(6):698-705.e2. doi: 10.1016/j.cllc.2017.05.004. Epub 2017 May 10.
Emergence of the T790M point mutation in exon 20 of the epidermal growth factor receptor (EGFR) is the most common mechanism of resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs). The aim of this study was to investigate the association between T790M mutation status and the progression patterns during EGFR-TKI treatment.
We reviewed 181 patients with advanced non-small-cell lung cancer harboring EGFR mutation, who were evaluated for T790M mutation status after initial EGFR-TKI failure (gefitinib, erlotinib, or afatinib). We retrospectively investigated the patient characteristics, initial EGFR-TKI response, T790M mutation status, subsequent treatment after initial EGFR-TKIs, timing of re-biopsy, and progression patterns during the EGFR-TKI treatment.
After the resistance to the EGFR-TKIs, the T790M mutation was identified in 87 (48%) of 181 patients. Seventy-three (40%) patients had solitary lesion progression, and 108 (60%) had multiple lesion progression during the initial EGFR-TKI treatment. The prevalence of the T790M mutation was significantly greater in patients with solitary lesion progression than those with multiple lesion progression (58% vs. 24%; P < .0001). The overall response rate and progression-free survival on initial EGFR-TKIs were significantly better in patients who acquired T790M after failure of EGFR-TKIs than those without T790M (overall response rate, 80% vs. 60%; P = .0033 and progression-free survival, 11.4 vs. 9.3 months; P = .0050). The multivariate analysis showed that gender, initial EGFR-TKI response, and progression patterns were significantly associated with T790M mutation status.
The progression patterns during initial EGFR-TKIs and initial EGFR-TKI response are associated with the T790M mutation.
表皮生长因子受体（EGFR）外显子 20 中的 T790M 点突变是 EGFR 酪氨酸激酶抑制剂（EGFR-TKIs）耐药的最常见机制。本研究旨在探讨 EGFR-TKI 治疗过程中 T790M 突变状态与进展模式之间的关系。
我们回顾性分析了 181 例携带 EGFR 突变的晚期非小细胞肺癌患者，这些患者在初始 EGFR-TKI 治疗失败后（吉非替尼、厄洛替尼或阿法替尼）评估 T790M 突变状态。我们回顾性调查了患者特征、初始 EGFR-TKI 反应、T790M 突变状态、初始 EGFR-TKIs 后后续治疗、再次活检时间以及 EGFR-TKI 治疗期间的进展模式。
在对 EGFR-TKIs 产生耐药性后，在 181 例患者中有 87 例（48%）检测到 T790M 突变。73 例（40%）患者出现孤立性病变进展，108 例（60%）患者在初始 EGFR-TKI 治疗期间出现多发性病变进展。在初始 EGFR-TKI 治疗期间，孤立性病变进展患者中 T790M 突变的发生率明显高于多发性病变进展患者（58% vs. 24%；P<0.0001）。在 EGFR-TKIs 失败后获得 T790M 的患者与未获得 T790M 的患者相比，初始 EGFR-TKIs 的总体缓解率和无进展生存期显著更好（总体缓解率，80% vs. 60%；P=0.0033 和无进展生存期，11.4 个月 vs. 9.3 个月；P=0.0050）。多变量分析表明，性别、初始 EGFR-TKI 反应和进展模式与 T790M 突变状态显著相关。
初始 EGFR-TKIs 期间的进展模式和初始 EGFR-TKI 反应与 T790M 突变相关。
