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Plasma ctDNA Kinetics as a Predictor of Systemic Therapy Response in Advanced NSCLC

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Hispanic bald man with a trimmed black and gray salt and pepper beard and black rimmed Wayfarer styled glasses, wearing a lab coat, in a dynamic lab scene with multiple scientists analyzing ctDNA samples and operating high-tech instruments, with the title Plasma ctDNA Kinetics: Predicting Treatment Response in Advanced NSCLC | Meta-Analysis Explained on a blue background

This image features a Hispanic bald man with a trimmed black and gray salt and pepper beard and black rimmed Wayfarer styled glasses, wearing a lab coat, positioned in a dynamic lab environment. He is surrounded by multiple scientists actively engaged in research, analyzing circulating tumor DNA (ctDNA) samples and operating advanced scientific instruments. Digital displays in the background show data related to non-small cell lung cancer (NSCLC) treatment outcomes. The title "Plasma ctDNA Kinetics: Predicting Treatment Response in Advanced NSCLC | Meta-Analysis Explained" is prominently displayed on a blue background, highlighting the focus on medical research and oncology breakthroughs.

Original Authors:  Luís F Leite da Silva, Erick F Saldanha, Júnior Samuel Alonso de Menezes, Leonardo Halamy Pereira, João Alexandre R de Bragança Dos Santos, Isabella Romagnoli Buonopane, Erito M de Souza, Caio Ulysses Galvani de Menezes, Gilberto Lopes

PMID: 39998904 | PMCID: PMC11853598 | DOI: 10.1093/oncolo/oyae344 | Date: March 03, 2025

Abstract

Background: Predicting early treatment response in advanced non-small cell lung cancer (NSCLC) is challenging. Longitudinal monitoring of circulating tumor DNA (ctDNA) can track tumor response to treatments like immune checkpoint blockade (ICB) and correlate with outcomes. This meta-analysis evaluated whether ctDNA clearance or decrease is associated with improved survival across various settings in NSCLC.

Methods: A systematic review of MEDLINE, EMBASE, and Cochrane databases (up to April 2024) identified studies evaluating the impact of ctDNA kinetics on survival outcomes in non-curative NSCLC settings. Pooled hazard ratios (HR) for progression-free survival (PFS) and overall survival (OS) were calculated using a random effects model.

Results: We included 32 studies with 3,047 NSCLC patients receiving systemic therapies such as targeted therapy (TT), ICB, and chemotherapy. Meta-analysis of 31 studies showed that ctDNA decrease/clearance was linked to improved PFS (HR: 0.32 [0.26, 0.40], I² = 63%, P < .01). Subgroup analysis indicated strong PFS benefits from ctDNA clearance (HR: 0.27 [0.20, 0.36]). Similar improvements were seen across patients undergoing targeted therapy (HR: 0.34) and ICB (HR: 0.33). Analysis of 25 studies revealed a significant association between ctDNA reduction and better OS (HR: 0.31 [0.23, 0.42], I² = 47%, P < .01). Subgroup findings were consistent for both TT (HR: 0.41) and ICB (HR: 0.32). Sensitivity analysis demonstrated that ctDNA clearance/decrease was consistently associated with improved PFS across study designs and ctDNA analysis methods. There was no significant variation in hazard ratios for PFS based on NSCLC subtypes, smoking status, or sex.

Conclusion: Plasma ctDNA kinetics was associated with improved survival outcomes in patients diagnosed with advanced NSCLC undergoing treatment with TT and ICB.

Key Findings

  • PFS Improvement: ctDNA decrease/clearance linked to better PFS (HR: 0.32).
  • OS Benefit: Significant association with improved OS (HR: 0.31).
  • Consistency: Benefits observed across targeted therapy (HR: 0.34) and ICB (HR: 0.33).
  • Robustness: No significant variation by NSCLC subtype, smoking status, or sex.

Implications

This study supports the potential of ctDNA kinetics as a reliable biomarker for monitoring NSCLC treatment response. Future research should focus on validating these findings across broader populations and therapy combinations.

References

Full study available at: DOI: 10.1093/oncolo/oyae344

PubMed: PMID: 39998904

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Related Articles:

Pashtoon Kasi MD, MS – The Role of Circulating Tumor DNA (ctDNA) in Colorectal Cancer Management – ASCO GI 2025
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