Yue Zhou, Lin Peng, Fei Liang, Li Chu, Xiao Chu, Xi Yang, Junhua Zhang, Tiantian Guo, Shanshan Jiang, Yechun Pang, Zezhou Wang, Li Zhang, Jianjiao Ni, Zhengfei Zhu
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Consolidative SRT was performed and EGFR-TKIs were not held during SRT. The primary endpoint was progression-free survival (PFS) and the secondary endpoints included overall survival and treatment-related adverse events (TRAEs). A prespecified propensity score matched (PSM) comparison was conducted with a contemporary cohort of patients who developed ORD but received EGFR-TKIs alone. This trial was registered with ClinicalTrails.gov, NCT04764214.</p><p><strong>Findings: </strong>All patients received consolidative SRT. With a median follow-up of 21.1 months, the median PFS was 29.9 (80% CI 22.4-32.4) months and the lower boundary exceeded the predefined threshold, meeting the primary endpoint. TRAEs occurred in 43 (70%) patients, with pneumonitis (27.9%) and esophagitis (26.2%) being the most common toxicities. Four patients (6.6%) reported grade ≥3 TRAEs, each for pneumonitis, esophagitis, leukopenia, and cranial radiation necrosis. PSM analysis showed significantly prolonged PFS in EGFR-TKI + SRT group compared to EGFR-TKI group (HR 0.46, 80% CI 0.20-0.61; <i>p</i> = 0.002).</p><p><strong>Interpretation: </strong>Consolidative SRT is associated with an encouraging PFS in first-line third-generation EGFR-TKI-treated metastatic NSCLC patients harboring ORD, with generally acceptable toxicities. Further confirmatory studies are warranted.</p><p><strong>Funding: </strong>Hui Lan Public Welfare and the Chinese Society of Clinical Oncology Foundation.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"76 ","pages":"102853"},"PeriodicalIF":9.6000,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11470411/pdf/","citationCount":"0","resultStr":"{\"title\":\"Safety and efficacy of consolidative stereotactic radiotherapy for oligo-residual EGFR-mutant non-small cell lung cancer after first-line third-generation EGFR-tyrosine kinase inhibitors: a single-arm, phase 2 trial.\",\"authors\":\"Yue Zhou, Lin Peng, Fei Liang, Li Chu, Xiao Chu, Xi Yang, Junhua Zhang, Tiantian Guo, Shanshan Jiang, Yechun Pang, Zezhou Wang, Li Zhang, Jianjiao Ni, Zhengfei Zhu\",\"doi\":\"10.1016/j.eclinm.2024.102853\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Prospective data is limited on the efficacy and safety of consolidative stereotactic radiotherapy (SRT) in metastatic epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients harboring oligo-residual disease (ORD) after first-line third-generation EGFR-tyrosine kinase inhibitors (TKIs).</p><p><strong>Methods: </strong>In this single-arm, phase II trial, 61 patients from two academic centers were enrolled from March 2021 to March 2023. 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引用次数: 0
摘要
背景：关于表皮生长因子受体（EGFR）突变的转移性非小细胞肺癌（NSCLC）患者在接受一线三代表皮生长因子受体酪氨酸激酶抑制剂（TKIs）治疗后罹患少残留疾病（ORD）的巩固性立体定向放射治疗（SRT）的疗效和安全性，前瞻性数据十分有限：在这项单臂II期试验中，来自两个学术中心的61名患者在2021年3月至2023年3月期间入组。所有这些患者均为转移性表皮生长因子受体突变型 NSCLC，且在一线使用第三代表皮生长因子受体抑制剂（EGFR-TKIs）后出现 ORD。患者接受了综合 SRT 治疗，在 SRT 治疗期间不再使用 EGFR-TKIs 治疗。主要终点是无进展生存期（PFS），次要终点包括总生存期和治疗相关不良事件（TRAEs）。该试验还与发生 ORD 但只接受 EGFR-TKIs 治疗的当代患者队列进行了预设倾向评分匹配（PSM）比较。该试验已在ClinicalTrails.gov上注册，编号为NCT04764214.Findings：所有患者均接受了SRT巩固治疗。中位随访时间为21.1个月，中位PFS为29.9个月（80% CI 22.4-32.4），下限超过了预定阈值，达到了主要终点。43名患者（70%）发生了TRAE，最常见的毒性反应是肺炎（27.9%）和食道炎（26.2%）。4名患者（6.6%）报告了≥3级TRAE，分别为肺炎、食管炎、白细胞减少症和颅骨放射性坏死。PSM分析显示，与EGFR-TKI组相比，EGFR-TKI+SRT组的PFS明显延长（HR 0.46，80% CI 0.20-0.61；P = 0.002）：解读：在一线接受第三代表皮生长因子受体-TKI治疗的携带ORD的转移性NSCLC患者中，综合SRT与令人鼓舞的PFS相关，且毒性一般可接受。还需要进一步的确证研究：惠兰公益和中国临床肿瘤学会基金会。
Safety and efficacy of consolidative stereotactic radiotherapy for oligo-residual EGFR-mutant non-small cell lung cancer after first-line third-generation EGFR-tyrosine kinase inhibitors: a single-arm, phase 2 trial.
Background: Prospective data is limited on the efficacy and safety of consolidative stereotactic radiotherapy (SRT) in metastatic epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients harboring oligo-residual disease (ORD) after first-line third-generation EGFR-tyrosine kinase inhibitors (TKIs).
Methods: In this single-arm, phase II trial, 61 patients from two academic centers were enrolled from March 2021 to March 2023. All these patients had metastatic EGFR-mutant NSCLC and harbored ORD after first-line third-generation EGFR-TKIs. Consolidative SRT was performed and EGFR-TKIs were not held during SRT. The primary endpoint was progression-free survival (PFS) and the secondary endpoints included overall survival and treatment-related adverse events (TRAEs). A prespecified propensity score matched (PSM) comparison was conducted with a contemporary cohort of patients who developed ORD but received EGFR-TKIs alone. This trial was registered with ClinicalTrails.gov, NCT04764214.
Findings: All patients received consolidative SRT. With a median follow-up of 21.1 months, the median PFS was 29.9 (80% CI 22.4-32.4) months and the lower boundary exceeded the predefined threshold, meeting the primary endpoint. TRAEs occurred in 43 (70%) patients, with pneumonitis (27.9%) and esophagitis (26.2%) being the most common toxicities. Four patients (6.6%) reported grade ≥3 TRAEs, each for pneumonitis, esophagitis, leukopenia, and cranial radiation necrosis. PSM analysis showed significantly prolonged PFS in EGFR-TKI + SRT group compared to EGFR-TKI group (HR 0.46, 80% CI 0.20-0.61; p = 0.002).
Interpretation: Consolidative SRT is associated with an encouraging PFS in first-line third-generation EGFR-TKI-treated metastatic NSCLC patients harboring ORD, with generally acceptable toxicities. Further confirmatory studies are warranted.
Funding: Hui Lan Public Welfare and the Chinese Society of Clinical Oncology Foundation.
期刊介绍：
eClinicalMedicine is a gold open-access clinical journal designed to support frontline health professionals in addressing the complex and rapid health transitions affecting societies globally. The journal aims to assist practitioners in overcoming healthcare challenges across diverse communities, spanning diagnosis, treatment, prevention, and health promotion. Integrating disciplines from various specialties and life stages, it seeks to enhance health systems as fundamental institutions within societies. With a forward-thinking approach, eClinicalMedicine aims to redefine the future of healthcare.
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