ArticleJTO clinical and research reports2025
Evaluating Circulating Tumor DNA Clearance as an Early Intermediate End Point Predicting Clinical Benefit in Metastatic Nonsquamous NSCLC After First-Line Chemoimmunotherapy.
Article in JTO clinical and research reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
2 citing papers in PubMed.
- Should we optimise or revise the management of initially unresectable stage III non-small cell lung cancer: rethinking consolidation therapy.Journal of the National Cancer Center · 2026Article
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Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Introduction: In the first-line (1L) NSCLC setting, overall survival (OS) as a trial end point is increasingly challenging due to longer survival and confounding from novel later-line therapies. This study aims to evaluate whether circulating tumor DNA (ctDNA) clearance (alone or with radiographic response) is a reliable early surrogate end point for progression-free survival (PFS) and OS in 1L NSCLC studies. Methods: Data from a phase III trial (IMpower150) of patients with untreated metastatic nonsquamous NSCLC were used. ctDNA clearance, unconfirmed radiographic response, and confirmed radiographic response at approximately 6 months after treatment were evaluated as surrogates for PFS and OS. The meta-analytic approaches were used. The data were randomly split into four cohorts, treating each as an independent "trial" to simulate a multi-trial meta-analysis. This process was repeated 50 times for statistical robustness. Results: ctDNA decline correlated with longer PFS and OS, with greater declines associated with better outcomes. Patients achieving ctDNA clearance (CL) by week 21 had the most significant PFS and OS improvements ( Conclusion: ctDNA decline is associated with improved survival outcomes in a clear dose-response manner. ctDNA clearance and radiologic response provide complementary prognostic information, and combining these end points (ctDNA_CL + Resp) can further improve prediction of PFS and OS. This combination also enhanced the correlation between treatment effects on the early end points and PFS/OS at the trial level. However, their overall ability to predict treatment effects at the trial level remained modest for both PFS and OS, likely due to the limited data from a single study. Further validation in larger, multi-trial data sets is needed to establish ctDNA clearance as a reliable early surrogate end point in first-line NSCLC.
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Registered trials
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