SCI

21 August 2024

Tyrosine Kinase Inhibitors With and Without Up-Front Stereotactic Radiosurgery for Brain Metastases From EGFR and ALK Oncogene-Driven Non-Small Cell Lung Cancer (TURBO-NSCLC)

（Journal of clinical oncology；IF：42.1）

  • Pike LRG, Miao E, Boe LA, Patil T, Imber BS, Myall NJ, Pollom EL, Hui C, Qu V, Langston J, Chiang V, Grant M, Goldberg SB, Palmer JD, Prasad RN, Wang TJC, Lee A, Shu CA, Chen LN, Thomas NJ, Braunstein SE, Kavanagh BD, Camidge DR, Rusthoven CG. Tyrosine Kinase Inhibitors With and Without Up-Front Stereotactic Radiosurgery for Brain Metastases From EGFR and ALK Oncogene-Driven Non-Small Cell Lung Cancer (TURBO-NSCLC). J Clin Oncol. 2024 Jul 24:JCO2302668. doi: 10.1200/JCO.23.02668. Epub ahead of print. PMID: 39047224.

  • CORRESPONDING AUTHOR ：Chad G. Rusthoven, MD

    Department of Radiation Oncology, University of Colorado, Aurora, CO.

    e-mail: chad.rusthoven@cuanschutz.edu.

Purpose 目的

Newer-generation tyrosine kinase inhibitors (TKIs) for non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements have demonstrated high CNS activity. The optimal use of up-front stereotactic radiosurgery (SRS) for brain metastases (BM) in patients eligible for CNS-penetrant TKIs is controversial, and data to guide patient management are limited.

新一代针对表皮生长因子受体（EGFR）突变和间变性淋巴瘤激酶（ALK）重排的非小细胞肺癌（NSCLC）酪氨酸激酶抑制剂（TKIs）已显示出较高的中枢神经系统（CNS）活性。在适合使用可穿透中枢神经系统的TKIs的患者中，是否应优先使用立体定向放射外科（SRS）治疗脑转移（BM）仍存在争议，且目前缺乏足够的数据来指导患者管理。

 

Materials and methods 材料与方法

Data on TKI-naïve patients with EGFR- and ALK-driven NSCLC with BM treated with CNS-penetrant TKIs with and without up-front SRS were retrospectively collected from seven academic centers in the United States. Time-to-CNS progression and overall survival (OS) were analyzed, with multivariable adjustment in Fine & Gray and Cox proportional hazards models for clinically relevant factors.

回顾性收集了来自美国七个学术中心的TKI初治、伴有脑转移的EGFR和ALK驱动型非小细胞肺癌（NSCLC）患者的数据，这些患者接受了可穿透中枢神经系统的TKIs治疗，部分患者同时接受了立体定向放射外科治疗（SRS）。对中枢神经系统进展时间和总生存期（OS）进行了分析，并在Fine & Gray模型和Cox比例风险模型中对临床相关因素进行了多变量调整。

 

Results 结果

From 2013 to 2022, 317 patients were identified (200 TKI-only and 117 TKI + SRS). Two hundred fifty (79%) and 61 (19%) patients received osimertinib and alectinib, respectively. Patients receiving TKI + SRS were more likely to have BM ≥1 cm (P < .001) and neurologic symptoms (P < .001) at presentation. Median OS was similar between the TKI and TKI + SRS groups (median 41 v40 months, respectively; P = .5). On multivariable analysis, TKI + SRS was associated with a significant improvement in time-to-CNS progression (hazard ratio [HR], 0.63 [95% CI, 0.42 to 0.96]; P = .033). Local CNS control was significantly improved with TKI + SRS (HR, 0.30 [95% CI, 0.16 to 0.55]; P < .001), whereas no significant differences were observed in distant CNS control. Subgroup analyses demonstrated a greater benefit from TKI + SRS in patients with BM ≥1 cm in diameter for time-to-CNS progression and CNS progression-free survival.

在2013年至2022年期间，共纳入了317名患者（200名仅接受TKI治疗，117名接受TKI联合SRS治疗）。其中，250名（79%）患者接受了奥希替尼（osimertinib）治疗，61名（19%）患者接受了阿来替尼（alectinib）治疗。接受TKI联合SRS治疗的患者在初诊时更可能具有≥1 cm的脑转移病灶（P < .001）和神经症状（P < .001）。TKI组和TKI联合SRS组的中位总生存期（OS）相似（分别为41个月和40个月；P = .5）。在多变量分析中，TKI联合SRS显著延长了中枢神经系统进展时间（风险比[HR]为0.63 [95% CI, 0.42至0.96]；P = .033）。TKI联合SRS显著提高了局部中枢神经系统的控制率（HR为0.30 [95% CI, 0.16至0.55]；P < .001），而远处中枢神经系统的控制率未见显著差异。亚组分析显示，对于直径≥1 cm的脑转移患者，TKI联合SRS在中枢神经系统进展时间和中枢神经系统无进展生存期方面有更大的获益。

 

Conclusion 结论

The addition of up-front SRS to CNS-penetrant TKI improved time-to-CNS progression and local CNS control, but not OS, in patients with BM from EGFR- and ALK-driven NSCLC. Patients with larger BM (≥1 cm) may benefit the most from up-front SRS.

在EGFR和ALK驱动的非小细胞肺癌伴脑转移的患者中，联合早期SRS和可穿透中枢神经系统的TKI治疗改善了中枢神经系统进展时间和局部中枢神经系统控制率，但未改善总生存期（OS）。对于较大脑转移病灶（≥1 cm）的患者，早期SRS可能带来更大的获益。