Chen Hongru, Yu Lu, Liang Fei, Zhou Yue, Chu Li, Chu Xiao, Yang Xi, Zhang Junhua, Pang Yechun, Wang Zezhou, Yuan Zhiyong, Ni Jianjiao, Zhu Zhengfei
Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
PLoS Med. 2025 Aug 1;22(8):e1004680. doi: 10.1371/journal.pmed.1004680. eCollection 2025 Aug.
Retrospective evidence indicated potential survival benefit of consolidative stereotactic radiotherapy (SRT) in patients with metastatic driver mutation-negative non-small cell lung cancer (NSCLC) harboring oligo-residual disease (ORD) after effective immune checkpoint inhibitor treatment. However, prospective data about consolidative SRT in this disease population after first-line chemoimmunotherapy remains scarce.
From March 2021 to March 2023, 59 patients (94.92% males) with metastatic driver mutation-negative NSCLC harboring ORD after effective first-line chemoimmunotherapy were enrolled in this single-arm, phase 2 trial (NCT04767009), which was conducted at Fudan University Shanghai Cancer Center, Shanghai, China. The median (interquartile range) age was 64 (57,71) years. All of the patients received extracranial and/or cranial SRT covering all of the oligo-residual lesions, without holding the maintenance systemic therapy during SRT. The most common sites targeted by consolidative SRT included the lung (n = 30), lymph nodes (n = 26), bone (n = 22), and brain (n = 22). All efficacy and safety analyses followed the intention-to-treat principle with all 59 enrolled patients included. No patient was lost to follow-up. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS) and treatment-related adverse events (TRAEs). With a median follow-up of 14.8 months, the median PFS was 29.0 (90% CI [13.97, Not Reach]) months, meeting the primary endpoint. The 2-year OS rate was 88.9% (95% CI [75.9%,100%]). TRAEs of any grade and grade ≥3 occurred in 58 (98.31%) and 13 (22.03%) patients, respectively. Moreover, a prespecified propensity score-matched comparison was conducted with a contemporary cohort of patients who developed ORD but received systematic therapy alone, which found that incorporating consolidative SRT was associated with prolonged PFS (adjusted HR 0.286, P < 0.001) and OS (adjusted HR 0.229, P = 0.023). The main methodological limitation of this single-arm trial is its inability to establish causal relationships and the findings require validation in randomized controlled trials.
Consolidative SRT was associated with prolonged PFS and generally acceptable toxicities in first-line chemoimmunotherapy-treated patients with metastatic NSCLC harboring ORD, supported by propensity-matched comparisons with a contemporary cohort.
回顾性证据表明，对于转移性驱动基因突变阴性的非小细胞肺癌（NSCLC）患者，在接受有效的免疫检查点抑制剂治疗后出现寡残留疾病（ORD），巩固性立体定向放射治疗（SRT）可能具有生存获益。然而，关于一线化疗免疫治疗后该疾病人群巩固性SRT的前瞻性数据仍然稀缺。
2021年3月至2023年3月，59例（94.92%为男性）转移性驱动基因突变阴性的NSCLC患者在接受有效的一线化疗免疫治疗后出现ORD，被纳入这项单臂2期试验（NCT04767009），该试验在中国上海复旦大学附属肿瘤医院进行。中位（四分位间距）年龄为64（57，71）岁。所有患者均接受颅外和/或颅内SRT，覆盖所有寡残留病灶，在SRT期间不进行维持性全身治疗。巩固性SRT最常靶向的部位包括肺（n = 30）、淋巴结（n = 26）、骨（n = 22）和脑（n = 22）。所有疗效和安全性分析均遵循意向性分析原则，纳入全部59例入组患者。无患者失访。主要终点为无进展生存期（PFS）。次要终点包括总生存期（OS）和治疗相关不良事件（TRAEs）。中位随访14.8个月，中位PFS为29.0（90%CI[13.97，未达到]）个月，达到主要终点。2年OS率为88.9%（95%CI[75.9%，100%]）。任何级别和≥3级TRAEs分别发生在58例（98.31%）和13例（22.03%）患者中。此外，与同期出现ORD但仅接受系统治疗的患者队列进行了预设的倾向评分匹配比较，结果发现纳入巩固性SRT与延长PFS（调整后HR 0.286，P<0.001）和OS（调整后HR 0.229，P = 0.023）相关。这项单臂试验的主要方法学局限性在于无法建立因果关系，研究结果需要在随机对照试验中进行验证。
在一线化疗免疫治疗的转移性NSCLC伴ORD患者中，巩固性SRT与延长PFS相关，且毒性一般可接受，倾向评分匹配比较与同期队列的结果支持这一结论。
