奥希替尼与第一代 EGFR 酪氨酸激酶抑制剂（TKI）在未经 TKI 治疗的伴脑膜转移的表皮生长因子受体突变型非小细胞肺癌中的临床结局比较。
Comparison of clinical outcomes of osimertinib and first-generation EGFR-tyrosine kinase inhibitors (TKIs) in TKI-untreated EGFR-mutated non-small-cell lung cancer with leptomeningeal metastases.
机构信息
Department of Thoracic Oncology, National Cancer Center Hospital, Chuo-ku, Tokyo; Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, Minato-ku, Tokyo.
Department of Thoracic Oncology, National Cancer Center Hospital, Chuo-ku, Tokyo; Department of Experimental Therapeutics, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan.
出版信息
ESMO Open. 2023 Aug;8(4):101594. doi: 10.1016/j.esmoop.2023.101594. Epub 2023 Jul 28.
BACKGROUND
Leptomeningeal metastases (LM) are devastating complications of epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC). Although osimertinib, a third-generation EGFR-tyrosine kinase inhibitor (TKI), has better penetration into the central nervous system than first-generation EGFR-TKIs, data on the distinct activity of EGFR-TKIs in untreated advanced EGFR-mutated NSCLC with LM are lacking.
PATIENTS AND METHODS
We retrospectively reviewed patients treated with EGFR-TKIs for TKI-untreated common EGFR-mutated NSCLC with LM between July 2002 and July 2021 at the National Cancer Center Hospital. The patients were divided into two groups: patients treated with osimertinib (Osi group) and those treated with gefitinib or erlotinib [first-generation (1G)-TKI group].
RESULTS
Of the 967 patients, 71 were eligible, including 29 in the Osi group and 42 in the 1G-TKI group. The median progression-free survival (PFS) and overall survival (OS) in the Osi group were better than those in the 1G-TKI group (PFS: 16.9 months versus 8.6 months, P = 0.007, and OS: 26.6 months versus 20.0 months, P = 0.158). The LM-overall response rate (ORR) and LM-PFS were significantly better in the Osi group than in the 1G-TKI group (LM-ORR: 62.5% versus 25.7%, P = 0.007; LM-PFS: 23.4 months versus 12.1 months, P = 0.021). In the subgroup analysis of EGFR mutation status, LM-PFS for patients with exon 19 deletion was significantly longer in the Osi group than in the 1G-TKI group (32.7 months versus 13.4 months, P = 0.013), whereas those with L858R mutation in exon 21 did not differ between the two groups. In the multivariate analysis, osimertinib and exon 19 deletion were significant factors for better LM-PFS and OS.
CONCLUSION
Osimertinib can be more effective for untreated common EGFR-mutated NSCLC patients with LM, especially those with exon 19 deletion, compared to first-generation TKIs.
背景
脑膜转移（LM）是表皮生长因子受体（EGFR）突变型非小细胞肺癌（NSCLC）的毁灭性并发症。尽管第三代 EGFR 酪氨酸激酶抑制剂（TKI）奥希替尼比第一代 EGFR-TKI 具有更好的中枢神经系统穿透力，但缺乏未经治疗的晚期 EGFR 突变型 NSCLC 伴 LM 患者中 EGFR-TKI 确切活性的数据。
患者和方法
我们回顾性分析了 2002 年 7 月至 2021 年 7 月在国家癌症中心医院接受 EGFR-TKI 治疗的未经 TKI 治疗的常见 EGFR 突变型 NSCLC 伴 LM 的患者。患者分为奥希替尼治疗组（Osi 组）和吉非替尼或厄洛替尼治疗组（第一代[1G]-TKI 组）。
结果
967 例患者中，71 例符合条件，包括 Osi 组 29 例，1G-TKI 组 42 例。Osi 组的中位无进展生存期（PFS）和总生存期（OS）均优于 1G-TKI 组（PFS：16.9 个月比 8.6 个月，P=0.007，OS：26.6 个月比 20.0 个月，P=0.158）。Osi 组的 LM 总体缓解率（ORR）和 LM-PFS 明显优于 1G-TKI 组（LM-ORR：62.5%比 25.7%，P=0.007；LM-PFS：23.4 个月比 12.1 个月，P=0.021）。在 EGFR 突变状态的亚组分析中，Osi 组患者的 exon19 缺失 LM-PFS 明显长于 1G-TKI 组（32.7 个月比 13.4 个月，P=0.013），而 21 号外显子 L858R 突变患者两组之间无差异。多因素分析显示，奥希替尼和 exon19 缺失是 LM-PFS 和 OS 更好的显著因素。
结论
与第一代 TKI 相比，奥希替尼可为未经治疗的常见 EGFR 突变型 NSCLC 伴 LM 患者，特别是伴有 exon19 缺失的患者，提供更有效的治疗。
Zotero 插件