William J. Magnuson, Nataniel H. Lester-Coll, Scott N. Gettinger, Joseph N. Contessa, James B. Yu, and Veronica L. Chiang, Yale School of Medicine, New Haven, CT; Abraham J. Wu, T. Jonathan Yang, Natalie A. Lockney, Naamit K. Gerber, and Kathryn Beal, Memorial Sloan Kettering Cancer Center, New York, NY; Arya Amini, Tejas Patil, Brian D. Kavanagh, and D. Ross Camidge, University of Colorado School of Medicine, Denver, CO; Steven E. Braunstein and Lauren C. Boreta, University of California-San Francisco, San Francisco, CA; Suresh K. Balasubramanian and Manmeet S. Ahluwalia, Cleveland Clinic Foundation, Cleveland, OH; and Niteshkumar G. Rana and Albert Attia, Vanderbilt University School of Medicine, Nashville, TN.
J Clin Oncol. 2017 Apr 1;35(10):1070-1077. doi: 10.1200/JCO.2016.69.7144. Epub 2017 Jan 23.
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.
立体定向放射外科手术（SRS）、全脑放疗（WBRT）和表皮生长因子受体（EGFR）-酪氨酸激酶抑制剂（TKI）是治疗 EGFR 突变型非小细胞肺癌（NSCLC）脑转移患者的选择。这项多机构分析旨在确定未接受 EGFR-TKI 治疗的 EGFR 突变型 NSCLC 患者发生脑转移后的最佳治疗方案。
来自 6 家机构的 351 名 EGFR 突变型 NSCLC 患者发生脑转移，符合本研究的纳入标准。排除标准包括既往接受 EGFR-TKI 治疗、EGFR-TKI 耐药突变、WBRT/SRS 后未接受 EGFR-TKI 治疗或随访时间不足。患者在颅内进展时接受 SRS 后行 EGFR-TKI 治疗、WBRT 后行 EGFR-TKI 治疗或 EGFR-TKI 后行 SRS 或 WBRT。从脑转移日期开始测量总生存期（OS）和颅内无进展生存期。
SRS（n = 100）、WBRT（n = 120）和 EGFR-TKI（n = 131）队列的中位 OS 分别为 46、30 和 25 个月（P <.001）。多变量分析显示，SRS 与 EGFR-TKI、WBRT 与 EGFR-TKI、年龄、体能状态、EGFR 外显子 19 突变和无颅外转移与 OS 改善相关。尽管 SRS 和 EGFR-TKI 队列具有相似的预后特征，但 WBRT 队列更可能预后不良（P =.001）。
这项多机构分析表明，在发生脑转移的 EGFR 突变型 NSCLC 患者中， upfront 使用 EGFR-TKI 和延迟放疗与 OS 较差相关。SRS 后行 EGFR-TKI 治疗可获得最长的 OS，并可避免 WBRT 的潜在神经认知后遗症。迫切需要开展一项前瞻性、多机构随机试验，比较 SRS 后行 EGFR-TKI 治疗与颅内进展时行 EGFR-TKI 后行 SRS 治疗的疗效。
