22 April 2025 : Review article
A Review of Circulating Tumor DNA (ctDNA) and the Liquid Biopsy in Cancer Diagnosis, Screening, and Monitoring Treatment Response
Dinah V. Parums1DEF*DOI: 10.12659/MSM.949300
Med Sci Monit 2025; 31:e949300
Table 3 Completed clinical trials in 2025 of the role of circulating tumor DNA (ctDNA) in solid tumor diagnosis and monitoring [23–37].
| Study/Clinical trial | Aims | No. of patients | ctDNA methods | Results |
|---|---|---|---|---|
| BFAST(NCT03178552)[,]23 | Relationship between blood-based genetic changes and targeted therapies in advanced NSCLC | 2219 | NGS | The application of blood-based NGS informed clinical decision-making |
| Liquid-Lung-A(NCT0262952)[]25 | Efficacy of afatinib in treatment-naïve NSCLC patients with exon 19 deletions or exon 21 point mutations | 331 | PCR (PANA Mutyper R assay) | Afatinib showed similar ORR and PFS in patients with lung cancer and mutations. Survival benefit of afatinib treatment achieved |
| Liquid-Lung-O(NCT0276928)[]26 | Treatment efficacy of osimertinib in patients with NSCLC with activating mutations (cohort 1) or T790M mutations (cohort 2) detected by ctDNA | 119 | PCR (PANA Mutyper R EGFR assay and Cobas Mutation Test v2) | Osimertinib had favorable outcomes in first-line treatment of metastatic NSCLC Osimertinib had favorable outcomes in patients with NSCLC with T790M mutations |
| APPLE(NCT0285689)[]27 | Feasibility of using longitudinal plasma T790M monitoring to determine treatment (gefitinib and osimertinib) | 103 | PCR (Cobas mutation test v2) | Serial monitoring of ctDNA T790M status was feasible and lead to the identification of molecular progression |
| ACCELERATE(NCT0486392)[]28 | Association between ctDNA genotyping before tissue diagnosis and time to treatment | 150 | NGS (InVisionFirst-Lung) | Use of plasma ctDNA genotyping before tissue diagnosis was associated with accelerated time to treatment |
| LOCAL(NCT03046316)[]29 | Feasibility of de-escalation of TKI treatment guided by ctDNA to achieve complete remission after local consolidative therapy | 60 | NGS (oncoMRD-B panel of 338 genes (GenePlus) | Overall, a ctDNA-guided adaptive de-escalation TKI treatment strategy was feasible for patients with advanced NSCLC |
| PlasmaMATCH(NCT03182634)[]30 | To determine the ability of ctDNA testing to select patients for mutation-directed therapy | 1034 | ddPCR and NGS (Guardant360) | Accurate genotyping identified mutation-specific treatments for breast cancer, including targeted therapies for uncommon and mutations |
| PADA-1(NCT03079011)[]31 | Effectiveness of early therapy change based on increasing mutation in blood, and safety of combining fulvestrant and palbociclib | 1017 | Multiplex ddPCR | Early therapeutic targeting of mutation in ER+/HER2-advanced breast cancer resulted in significant clinical benefit |
| ACTDNA(NCT05079074)[]32 | Efficacy of re-subtyping and determining treatment strategy based on ctDNA alterations | 223 | NGS | Patients with druggable ctDNA alterations showed significant improvements in PFS and disease control rate |
| c-TRAK-TN(NCT03145961)[]33 | Role of ctDNA in detecting residual disease following standard primary treatment for TNBC | 208 | ddPCR | High rate of metastatic disease on ctDNA detection, MRD detection, and personalized ctDNA assays clinically achievable |
| ASPECCT(NCT01001377)[]34 | To analyze mutations in cfDNA in plasma from patients with CRC treated with panitumumab | 261 | NGS | Genotyping identified that mutations were associated with poorer patient outcomes |
| CHRONOS(NCT0322792)[]35 | To identify mutations in ctDNA for a chemotherapy-free anti- re-challenge with panitumumab | 52 | NGS and ddPCR | ctDNA analysis was an effective, safe, and rapid method to guide anti- re-challenge therapy with panitumumab in patients with mCRC |
| DYNAMIC(ACTRN12615000381583)[]36 | To assess whether a ctDNA-guided approach could reduce the use of ACT without compromising recurrence risk | 455 | NGS (Safe-SeqS) | A ctDNA-guided approach reduced ACT use without compromising recurrence-free survival |
| COBRA(NCT0406810)[]37 | To evaluate whether positive ctDNA after resection could identify patients who will benefit from ACT | 635 | NGS (Guardant LUNAR assay) | No improvement in ctDNA clearance after 6 months of chemotherapy for patients with ctDNA detected following resection of stage IIA CRC |
| ACT – adjuvant chemotherapy; ACTRN – Australian New Zealand Clinical Trials Registry number; ctDNA – circulating tumor DNA; ddPCR – droplet digital PCR; ER – estrogen receptor; MBC – metastatic breast cancer; mCRC – metastatic colorectal cancer; MRD – minimal residual disease; NCT – National Clinical Trial (identifier number); NGS – next-generation sequencing; NSCLC – non-small cell lung cancer; OS – overall survival; PCR – polymerase chain reaction; PFS – progression-free survival; Safe-SeqS – Safe-Sequencing System; TNBC – triple-negative breast cancer; TKI – tyrosine kinase inhibitor; UMIN-CTR – University Hospital Medical Information Network Clinical Trials Registry. | ||||