In a systematic review and meta-analysis reported in The Oncologist, Leite da Silva et al found plasma circulating tumor DNA (ctDNA) kinetics to be predictive of survival outcomes in patients with advanced non–small cell lung cancer (NSCLC) who were undergoing targeted therapy and immune checkpoint blockade therapy.
“The results underscore the clinical relevance of longitudinal plasma ctDNA assessment in predicting survival for patients with advanced NSCLC,” the investigators commented. “Integrating ctDNA kinetics analysis into routine clinical practice is a promising noninvasive biomarker that can aid clinicians in timely therapeutic decisions.”
Study Details
The investigators conducted a systematic review of MEDLINE, Embase, and the Cochrane Central Register to identify studies that evaluated the impact of ctDNA kinetics on survival outcomes in noncurative NSCLC settings. Using a random effects model, they calculated pooled hazard ratios for progression-free and overall survival.
A total of 32 studies with 3,047 patients who had NSCLC and received systemic therapies (eg, targeted therapy, immune checkpoint blockade therapy, and chemotherapy) were ultimately included in the analysis.
Key Findings
Based on a meta-analysis of 31 studies, decrease or clearance of ctDNA was associated with improved progression-free survival (hazard ratio [HR] = 0.32; I2 = 63%; P < .01). Subgroup analysis revealed strong progression-free survival benefits from ctDNA clearance (HR = 0.27), according to the investigators. Similar improvements were observed across patients undergoing targeted therapy (HR = 0.34) and immune checkpoint blockade therapy (HR = 0.33).
Across 25 studies, reduction in ctDNA was shown to significantly correlate with better overall survival (HR = 0.31; I² = 47%; P < .01). Subgroup findings were found to be consistent for both targeted therapy (HR = 0.41) and immune checkpoint blockade therapy (HR = 0.32). Sensitivity analysis revealed that ctDNA clearance or decrease was consistently associated with improved progression-free survival across study designs and ctDNA analysis methods. The investigators reported no significant variation in hazard ratios for progression-free survival across NSCLC subtypes, smoking status, and sex.
The investigators concluded: “In our study, longitudinal or serial plasma ctDNA clearance or reduction was associated with improved survival outcomes in patients with advanced NSCLC undergoing targeted therapy and immune checkpoint blockade [therapy]. Our study results support the use of plasma ctDNA as an early endpoint in prospective clinical trials for further biomarker validation before incorporation in the clinical setting.”
Luís F. Leite da Silva, an MD/PhD candidate, of Universidade Federal Fluminense, Niterói, Brazil, is the corresponding author of the article in The Oncologist.
Disclosure: The authors declared that no financial support was received for the research, authorship, and/or publication of the article.
