Osimertinib for EGFR-Mutant Lung Cancer with Brain Metastases: Results from a Single-Center Retrospective Study
Osimertinib for EGFR-Mutant Lung Cancer with Brain Metastases: Results from a Single-Center Retrospective Study
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DOI：
10.1634/theoncologist.2018-0264
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发表时间：
2019-06-01
期刊：
影响因子：
5.8
通讯作者：
Neal, Joel W.
中科院分区：
文献类型：
--
作者：
Xie, Lijia;Nagpal, Seema;Neal, Joel W.
奥希替尼是第三代酪氨酸激酶抑制剂，最初获批用于表皮生长因子受体（EGFR）突变型非小细胞肺癌（NSCLC）伴T790 M获得性耐药，现已获批用于一线治疗。然而，支持奥希替尼用于未经治疗的脑转移瘤的数据有限，尽管它已确定了中枢神经系统（CNS）活性。我们的研究比较了接受颅骨放疗和奥希替尼治疗的进展性脑转移患者与单独接受奥希替尼治疗的患者的临床结局。方法通过检索电子病历数据库，确定2015年11月至2016年12月在斯坦福大学癌症中心接受奥希替尼治疗的40例患者。11例患者有进展性脑转移，未接受放疗（A组），9例患者有进展性脑转移，在开始奥希替尼治疗时接受放疗（B组），20例患者在开始奥希替尼治疗时有稳定的脑转移（C组）。回顾性评价三组患者和疾病特征、影像学反应和生存结局。结果中枢神经系统缓解率为32.3%。中位至治疗失败时间（TTF）、总无进展生存期（PFS）和总生存期（OS）分别为10.0个月（95%置信区间[CI]，4.5-11.8）、8.8个月（95% CI，6.2-12.1）和16.2个月。A组的中位TTF为15.1个月（95% CI，1.7-28.5），B组为7.7个月（95% CI，0-15.5），C组为10.7个月（95% CI，9.0-12.5）。A组的中位PFS为8.8个月（95% CI，4.3-13.4），B组未达到，C组为8.4个月（95% CI，5.6-11.1）。A组和C组未达到中位OS，B组为16.2个月。三组之间的TTF、PFS或OS无明显差异。结论：在我们的系列研究中，进展性脑转移患者在开始奥希替尼治疗前接受放疗不会延长TTF、PFS或OS。为了最大限度地降低放射相关毒性的风险，对于一些EGFR突变型NSCLC伴脑转移且最初对奥希替尼二线治疗有效的患者，可以考虑延迟放射治疗。奥希替尼是第三代表皮生长因子受体（EGFR）酪氨酸激酶抑制剂，最近被批准用于EGFR突变型非小细胞肺癌的一线治疗。虽然它似乎具有中枢神经系统（CNS）活性，但大多数临床试验都排除了未经治疗的进展性脑转移患者。本研究纳入了接受奥希替尼治疗的稳定和进展性CNS转移患者，发现接受奥希替尼单药治疗的患者与接受奥希替尼和放射外科治疗的患者相比，在至治疗失败的中位时间、至疾病进展的时间和总生存期方面无明显差异。这可能支持临床医生决定推迟对选定的未接受治疗的脑转移患者进行放射治疗，这些患者是奥希替尼治疗的候选者。
Introduction Osimertinib is a third-generation tyrosine kinase inhibitor, initially approved for epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) with T790M acquired resistance, and now approved in the first-line setting. However, data supporting the use of osimertinib in untreated brain metastases are limited, although it has established central nervous system (CNS) activity. Our study compares the clinical outcomes of patients experiencing progressing brain metastases treated with cranial irradiation and osimertinib with those treated with osimertinib alone. Methods Forty patients who were treated with osimertinib at the Stanford Cancer Center from November 2015 to December 2016 were identified by searching an electronic medical record database. Eleven patients had progressing brain metastases and did not receive radiation (group A), 9 patients had progressing brain metastases and received radiation when starting osimertinib (group B), and 20 patients had stable brain metastases at the time of initiating osimertinib (group C). Patient and disease characteristics, radiographic responses, and survival outcomes were evaluated retrospectively for the three groups. Results The CNS response rate was 32.3%. Median time to treatment failure (TTF), overall progression-free survival (PFS), and overall survival (OS) were 10.0 months (95% confidence interval [CI], 4.5-11.8), 8.8 months (95% CI, 6.2-12.1), and 16.2 months, respectively. Median TTF was 15.1 months for group A (95% CI, 1.7-28.5), 7.7 months for group B (95% CI, 0-15.5), and 10.7 months for group C (95% CI, 9.0-12.5). The median PFS was 8.8 months for group A (95% CI, 4.3-13.4), not reached for group B, and 8.4 months for group C (95% CI, 5.6-11.1). The median OS was not reached for group A and C, and was 16.2 months for group B. There was no apparent difference in TTF, PFS, or OS between the three groups. Conclusion Receiving radiation prior to starting osimertinib for patients with progressing brain metastases did not prolong TTF, PFS, or OS in our series. To minimize the risks of radiation-related toxicity, delaying radiation could be considered for some patients with EGFR-mutant NSCLC with brain metastases who initially respond to osimertinib in the second-line setting. Implications for Practice Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor recently approved for the first-line treatment of EGFR-mutant non-small cell lung cancer. Although it appears to have central nervous system (CNS) activity, most clinical trials have excluded patients with untreated, progressing brain metastases. This study included patients with stable and progressing CNS metastases treated with osimertinib and found no apparent differences in median time to treatment failure, time to progression, and overall survival in patients who received osimertinib alone compared with those who received osimertinib and radiosurgery. This may support a clinician's decision to defer radiation for selected patients with untreated brain metastases who are candidates for osimertinib therapy.