2567 - Stereotactic Radiotherapy Alone for Multiple Brain Metastases after Intracranial Progression in Patients with EGFR-Mutant Lung Adenocarcinoma Receiving EGFR-TKIs: A Multi-Center, Single Arm, Phase II

Y. Ma¹, J. Yi¹, P. Xing², W. Jiang³, H. Sun⁴, H. Zhu⁵, D. Li⁶, Q. Qiao⁷, X. Jiang⁸, R. Zhou⁹, and Y. Zhang¹; ¹Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, ²National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, ³Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China, Shenzhen, China, ⁴Cancer hospital, Chinese Academy of Medical Sciences, Shenzhen Center, Shenzhen, China, ⁵Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Science, Jinan, China, ⁶Department of Oncology, The General Hospital of Western Theater Command PLA, Chengdu, China, ⁷Department of Radiation Oncology, the First Hospital of China Medical University, Shenyang, China, ⁸Department of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun, China, ⁹Xiangya Hospital Central South University, Changsha, China

Purpose/Objective(s): A multi-center, single arm, phase II trial was conducted to investigate the intracranial efficacy and safety of SRT without WBRT for multiple BMs in EGFR-mutant lung adenocarcinoma pts after intracranial progression receiving EGFR-TKIs. Materials/

Methods: Patients with EGFR 19 deletion or 21 L858R mutant lung adenocarcinoma, who developed multiple BMs without extra-cranial progression after EGFR-TKIs, were enrolled. The regimens of SRT varied based on the volume and location of brain lesions. Sample size was calculated with PASS software, with the hypothetical 1-year intracranial progression free survival (IPFS) rate of 80%, ?=0.2, a=0.05 and drop-out rate of 10%. Finally, 78 pts was needed. The primary endpoint was 1-year IPFS rate after SRT, and the secondary endpoints included 1-year local control (LC), progression free survival (PFS), overall survival (OS) rates after SRT and SRT related toxicities. Survival rates were calculated using Kaplan-Meier method.
Results: From January 2020 to October 2023, 78 pts (male: female=28:50) were enrolled from 7 institutions, with the median age of 59 (range: 36-85) years old. Thirty-five pts (44.9%) had BMs at the initial diagnosis of NSCLC. Thirty-three pts (42.3%) took third generation EGFR-TKIs for initial treatment, and 45 pts (57.7%) received the first or second generation. The median intracranial progression time from TKIs was 15.9 months (0.2-64.3 months), and 25/45 pts changed TKIs before SRT. Thirty-two pts (41.0%) had symptomatic BMs when receiving SRT. The median BM number was 4 (2-20), while 22 pts (28.2%) had more than 4 lesions. The median largest diameter of BMs was 1.9 cm (0.4-3.0 cm). SRT regimens ranged from 20 Gy in 1 fraction to 52 Gy in 13 fractions. The median follow-up time after SRT was 28.3 months (1.6-46.6 months). The 1-year IPFS rate was 83.1%, with median IPFS of 33.5 months (95%CI 18.7-48.4 months). The 1-year LC, PFS and OS rates were 90.9%, 72.7% and 82.4%, respectively. The median PFS time was 21.8 months (95%CI 16.9-26.7 months) while median OS has not reached. No =Grade 3 SRT related toxicities has been observed.
Conclusion: This prospective trial demonstrated SRT poses favorable IPFS, PFS and OS with acceptable toxicities in multiple BMs pts with EGFR-mutant lung adenocarcinoma receiving EGFR-TKIs. This strategy delays EGFR-TKIs resistance. Further studies with larger sample size are warranted.