Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 71067Sun Yat-sen University Cancer Center, Guangzhou, China.
Cancer Control. 2022 Jan-Dec;29:10732748221081360. doi: 10.1177/10732748221081360.
Osimertinib has exhibited promising central nervous system (CNS) efficacy in Epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC) patients. In real-world clinical practice, patients would turn to plasma genotyping or take osimertinib blindly after CNS progression on previous tyrosine kinase inhibitors (TKIs). However, the efficacy of osimertinib in those patients according to their T790M mutational status has not been explored.
Twenty-five patients who received osimertinib due to intracranial progressions with stable extracranial diseases after early-generation EGFR-TKI treatment were collected from 1032 EGFR-mutated NSCLC. Plasma samples were analyzed for EGFR mutations using next-generation sequencing (NGS) or polymerase chain reaction (PCR).
Among the 25 patients, 17 patients took plasma genotyping before osimertinib treatment with 8 patients EGFR T790M mutation-positive and the rest started osimertinib blindly. The median progression-free survival (PFS) was 8.0 months (95% confidence interval [CI]: 6.12-9.94) and median intracranial PFS (iPFS) was 14.4 months (95% CI: 7.27-21.59) for the total population. No statistical difference was found in PFS and iPFS among patients with different EGFR T790M mutational statuses. Intracranial disease control rate (DCR) was 100.0% for 14 patients with evaluable intracranial lesions despite different T790M mutational statuses. DCR for extracranial lesions and overall lesions were 100.0%, 66.7%, and 87.5% for patients with T790M, no T790M, and unknown T790M mutational status, respectively.
For EGFR-mutated NSCLC patients with only intracranial progressions after previous TKI treatments, osimertinib is a promising treatment option regardless of T790M mutational status from plasma genotyping.
奥希替尼在表皮生长因子受体（EGFR）突变的晚期非小细胞肺癌（NSCLC）患者中显示出有前景的中枢神经系统（CNS）疗效。在真实世界的临床实践中，患者会在先前的酪氨酸激酶抑制剂（TKI）发生 CNS 进展后转向血浆基因分型或盲目使用奥希替尼。然而，根据 T790M 突变状态，奥希替尼在这些患者中的疗效尚未得到探索。
从 1032 例 EGFR 突变 NSCLC 中收集了 25 例因早期 EGFR-TKI 治疗后颅内进展但颅外疾病稳定而接受奥希替尼治疗的患者。使用下一代测序（NGS）或聚合酶链反应（PCR）对血浆样本进行 EGFR 突变分析。
在 25 例患者中，有 17 例患者在接受奥希替尼治疗前进行了血浆基因分型，其中 8 例患者 EGFR T790M 突变阳性，其余患者则盲目开始使用奥希替尼。总体人群的中位无进展生存期（PFS）为 8.0 个月（95%置信区间[CI]：6.12-9.94），中位颅内无进展生存期（iPFS）为 14.4 个月（95%CI：7.27-21.59）。不同 EGFR T790M 突变状态的患者之间的 PFS 和 iPFS 无统计学差异。尽管 T790M 突变状态不同，有可评估颅内病灶的 14 例患者的颅内疾病控制率（DCR）仍为 100.0%。T790M 阳性、无 T790M 和 T790M 未知的患者的颅外病灶和总病灶的 DCR 分别为 100.0%、66.7%和 87.5%。
对于先前 TKI 治疗后仅发生颅内进展的 EGFR 突变型 NSCLC 患者，奥希替尼是一种有前途的治疗选择，无论血浆基因分型的 T790M 突变状态如何。
