Consolidative stereotactic radiotherapy for oligo-residual non-small cell lung cancer after first-line chemoimmunotherapy: A single-arm, phase 2 trial from China.

<h4>Background</h4>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...

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Main Authors: Hongru Chen, Lu Yu, Fei Liang, Yue Zhou, Li Chu, Xiao Chu, Xi Yang, Junhua Zhang, Yechun Pang, Zezhou Wang, Zhiyong Yuan, Jianjiao Ni, Zhengfei Zhu
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-08-01
Series:PLoS Medicine
Online Access:https://doi.org/10.1371/journal.pmed.1004680
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author Hongru Chen
Lu Yu
Fei Liang
Yue Zhou
Li Chu
Xiao Chu
Xi Yang
Junhua Zhang
Yechun Pang
Zezhou Wang
Zhiyong Yuan
Jianjiao Ni
Zhengfei Zhu
author_facet Hongru Chen
Lu Yu
Fei Liang
Yue Zhou
Li Chu
Xiao Chu
Xi Yang
Junhua Zhang
Yechun Pang
Zezhou Wang
Zhiyong Yuan
Jianjiao Ni
Zhengfei Zhu
author_sort Hongru Chen
collection DOAJ
description <h4>Background</h4>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.<h4>Methods and findings</h4>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.<h4>Conclusions</h4>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.
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spelling doaj-art-c8f2a63082e34ee4ab5af26a58d139a32025-08-20T03:59:35ZengPublic Library of Science (PLoS)PLoS Medicine1549-12771549-16762025-08-01228e100468010.1371/journal.pmed.1004680Consolidative stereotactic radiotherapy for oligo-residual non-small cell lung cancer after first-line chemoimmunotherapy: A single-arm, phase 2 trial from China.Hongru ChenLu YuFei LiangYue ZhouLi ChuXiao ChuXi YangJunhua ZhangYechun PangZezhou WangZhiyong YuanJianjiao NiZhengfei Zhu<h4>Background</h4>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.<h4>Methods and findings</h4>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.<h4>Conclusions</h4>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.https://doi.org/10.1371/journal.pmed.1004680
spellingShingle Hongru Chen
Lu Yu
Fei Liang
Yue Zhou
Li Chu
Xiao Chu
Xi Yang
Junhua Zhang
Yechun Pang
Zezhou Wang
Zhiyong Yuan
Jianjiao Ni
Zhengfei Zhu
Consolidative stereotactic radiotherapy for oligo-residual non-small cell lung cancer after first-line chemoimmunotherapy: A single-arm, phase 2 trial from China.
PLoS Medicine
title Consolidative stereotactic radiotherapy for oligo-residual non-small cell lung cancer after first-line chemoimmunotherapy: A single-arm, phase 2 trial from China.
title_full Consolidative stereotactic radiotherapy for oligo-residual non-small cell lung cancer after first-line chemoimmunotherapy: A single-arm, phase 2 trial from China.
title_fullStr Consolidative stereotactic radiotherapy for oligo-residual non-small cell lung cancer after first-line chemoimmunotherapy: A single-arm, phase 2 trial from China.
title_full_unstemmed Consolidative stereotactic radiotherapy for oligo-residual non-small cell lung cancer after first-line chemoimmunotherapy: A single-arm, phase 2 trial from China.
title_short Consolidative stereotactic radiotherapy for oligo-residual non-small cell lung cancer after first-line chemoimmunotherapy: A single-arm, phase 2 trial from China.
title_sort consolidative stereotactic radiotherapy for oligo residual non small cell lung cancer after first line chemoimmunotherapy a single arm phase 2 trial from china
url https://doi.org/10.1371/journal.pmed.1004680
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