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《JCO》为什么非小细胞肺癌脑转移时应先放疗再使用EGFR TKI治疗

2017年01月30日

编译：南南和北北

来源：桓兴医讯

在未使用过酪氨酸激酶抑制剂、上皮生长因子受体突变的非小细胞肺癌中脑转移的治疗：一项回顾性多中心分析：关于立体定向放射外科治疗、全脑放射治疗和EGFR TKI的疗效比较。

美国《临床肿瘤杂志》（JCO）2017年1月23日在线先发表了一篇回顾性研究。在未使用过酪氨酸激酶抑制剂、上皮生长因子受体突变的非小细胞肺癌中脑转移的治疗：一项回顾性多中心分析

目的

对于上皮生长因子受体（EGFR）突变的非小细胞肺癌患者脑转移的治疗，可选择立体定向放射外科治疗、全脑放射治疗和上皮生长因子受体酪氨酸激酶抑制剂。这项多中心分析旨在研究EGFR突变的、未接受过EGFR酪氨酸激酶抑制剂的非小细胞肺癌患者出现脑转移时的最佳治疗选择。

材料和方法

来自6家医疗机构共计351名EGFR 突变的非小细胞肺癌患者出现脑转移，符合研究入组标准，剔除标准包括既往使用过EGFR酪氨酸激酶抑制剂、EGFR酪氨酸激酶抑制剂耐药突变、立体定向放射外科治疗/全脑放射治疗后未能接受EGFR酪氨酸激酶抑制剂治疗、或者随访不足。颅内进展时，对患者进行立体定向放射外科治疗后序贯EGFR酪氨酸激酶抑制剂治疗、全脑放射治疗后序贯EGFR酪氨酸激酶抑制剂治疗、或者EGFR酪氨酸激酶抑制剂治疗后序贯立体定向放射外科治疗或全脑放疗。从出现脑转移日期中测算出总生存期和颅内无进展生存期。

结果

立体定向放射外科治疗组、全脑放射治疗组和EGFR酪氨酸激酶抑制剂组的中位总生存期分别为46、30、25个月（P<0.001）。进行多变量分析，立体定向放射外科治疗对比EGFR酪氨酸激酶抑制剂、全脑放射治疗对比EGFR酪氨酸激酶抑制剂、年龄、体能状况、EGFR19外显子突变、无颅外转移灶这些因素与总生存期延长相关。立体定向放射外科治疗组和EGFR酪氨酸激酶抑制剂组的预后因素相当，全脑放疗组的预后因素则较差。

结论

这项多中心分析表明，在EGFR 突变的非小细胞肺癌患者出现脑转移时，首先使用EGFR酪氨酸激酶抑制剂、延期进行放射治疗与总生存差相关。立体定向放射外科治疗序贯EGFR酪氨酸激酶抑制剂治疗总生存期最长、可使患者避免全脑放疗可能引起的神经认知后遗症。目前急需进行一项前瞻性、多中心、随机化临床试验，在颅内进展时，对立体定向放射外科治疗序贯EGFR酪氨酸激酶抑制剂和EGFR酪氨酸激酶抑制剂序贯立体定向放射外科治疗进行对比。

《桓兴医讯》编译组南南和北北

Management of Brain Metastases in Tyrosine Kinase Inhibitor–Naïve Epidermal Growth Factor Receptor–Mutant Non–Small-Cell Lung Cancer: A Retrospective Multi-Institutional Analysis

William J. Magnuson, Nataniel H. Lester-Coll, Abraham J. Wu, T. Jonathan Yang, Natalie A. Lockney, Naamit K. Gerber, Kathryn Beal, Arya Amini, Tejas Patil, Brian D. Kavanagh, D. Ross Camidge, Steven E. Braunstein, Lauren C. Boreta, Suresh K. Balasubramanian, Manmeet S. Ahluwalia, Niteshkumar G. Rana, Albert Attia, Scott N. Gettinger, Joseph N. Contessa, James B. Yu, and Veronica L. Chiang

Purpose

Stereotactic radiosurgery (SRS), whole-brain radiotherapy (WBRT), and epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are treatment options for brain metastases in patients with EGFR-mutant non–small-cell lung cancer (NSCLC). This multi-institutional analysis sought to determine the optimal management of patients with EGFR-mutant NSCLC who develop brain metastases and have not received EGFR-TKI.

Materials and Methods

A total of 351 patients from six institutions with EGFR-mutant NSCLC developed brain metastases and met inclusion criteria for the study. Exclusion criteria included prior EGFR-TKI use, EGFR-TKI resistance mutation, failure to receive EGFR-TKI after WBRT/SRS, or insufficient follow-up. Patients were treated with SRS followed by EGFR-TKI, WBRT followed by EGFR-TKI, or EGFR-TKI followed by SRS or WBRT at intracranial progression. Overall survival (OS) and intracranial progression-free survival were measured from the date of brain metastases.

Results

The median OS for the SRS (n = 100), WBRT (n = 120), and EGFR-TKI (n = 131) cohorts was 46, 30, and 25 months, respectively (P < .001). On multivariable analysis, SRS versus EGFR-TKI, WBRT versus EGFR-TKI, age, performance status, EGFR exon 19 mutation, and absence of extracranial metastases were associated with improved OS. Although the SRS and EGFR-TKI cohorts shared similar prognostic features, the WBRT cohort was more likely to have a less favorable prognosis (P = .001).

Conclusion

This multi-institutional analysis demonstrated that the use of upfront EGFR-TKI, and deferral of radiotherapy, is associated with inferior OS in patients with EGFR-mutant NSCLC who develop brain metastases. SRS followed by EGFR-TKI resulted in the longest OS and allowed patients to avoid the potential neurocognitive sequelae of WBRT. A prospective, multi-institutional randomized trial of SRS followed by EGFR-TKI versus EGFR-TKI followed by SRS at intracranial progression is urgently needed.

参考文献：

http://ascopubs.org/doi/full/10.1200/JCO.2016.69.7144

编辑：肿瘤资讯-小编