AI Article Synopsis
- The study investigated how changes in circulating tumor DNA (ctDNA) levels can predict long-term outcomes in patients with estrogen receptor-positive metastatic breast cancer undergoing treatment with paclitaxel and an AKT inhibitor, capivasertib.
- Researchers analyzed ctDNA samples from a clinical trial to determine if early suppression of ctDNA could serve as a reliable early indicator of patient outcomes, specifically progression-free survival (PFS).
- Results indicated that ctDNA suppression after just 4 weeks of treatment was significantly associated with longer PFS, suggesting that monitoring ctDNA dynamics could be an effective method for predicting treatment efficacy in cancer patients.
Article Abstract
Background: Dynamic changes in circulating tumour DNA (ctDNA) levels may predict long-term outcome. We utilised samples from a phase I/II randomised trial (BEECH) to assess ctDNA dynamics as a surrogate for progression-free survival (PFS) and early predictor of drug efficacy.
Patients And Methods: Patients with estrogen receptor-positive advanced metastatic breast cancer (ER+ mBC) in the BEECH study, paclitaxel plus placebo versus paclitaxel plus AKT inhibitor capivasertib, had plasma samples collected for ctDNA analysis at baseline and at multiple time points in the development cohort (safety run-in, part A) and validation cohort (randomised, part B). Baseline sample ctDNA sequencing identified mutations for longitudinal analysis and mutation-specific digital droplet PCR (ddPCR) assays were utilised to assess change in ctDNA abundance (allele fraction) between baseline and 872 on-treatment samples. Primary objective was to assess whether early suppression of ctDNA, based on pre-defined criteria from the development cohort, independently predicted outcome in the validation cohort.
Results: In the development cohort, suppression of ctDNA was apparent after 8 days of treatment (P = 0.014), with cycle 2 day 1 (4 weeks) identified as the optimal time point to predict PFS from early ctDNA dynamics. In the validation cohort, median PFS was 11.1 months in patients with suppressed ctDNA at 4 weeks and 6.4 months in patients with high ctDNA (hazard ratio = 0.20, 95% confidence interval 0.083-0.50, P < 0.0001). There was no difference in the level of ctDNA suppression between patients randomised to capivasertib or placebo overall (P = 0.904) nor in the PIK3CA mutant subpopulation (P = 0.071). Clonal haematopoiesis of indeterminate potential (CHIP) was evident in 30% (18/59) baseline samples, although CHIP had no effect on tolerance of chemotherapy nor on PFS.
Conclusion: Early on-treatment ctDNA dynamics are a surrogate for PFS. Dynamic ctDNA assessment has the potential to substantially enhance early drug development.
Clinical Registration Number: NCT01625286.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6594458 | PMC |
| http://dx.doi.org/10.1093/annonc/mdz085 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Circulating Tumor Cell-Free DNA as Prognostic Biomarker in Non-Small Cell Lung Cancer Patients Undergoing Immunotherapy: The CORELAB Experience.
Int J Mol Sci
January 2025
Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, 50134 Florence, Italy.
The expression level of Programmed Death-Ligand 1 (PD-L1) determined by the immunohistochemical method is currently approved to test the potential efficacy of immune-checkpoint inhibitors and to candidate patients with Non-Small Cell Lung Cancer (NSCLC) for treatment with immunotherapeutic drugs. As part of the CORELAB (New prediCtivebiOmaRkers of activity and Efficacy of immune checkpoint inhibitors in advanced non-small cell Lung cArcinoma) project, aimed at identifying new predictive and prognostic biomarkers in NSCLC patients receiving immunotherapeutic drugs, we investigated the role of circulating tumor DNA (ctDNA) molecular characterization as an additional predictive biomarker. We analyzed plasma ctDNA by targeted Next Generation Sequencing in a subset of 50 patients at different time points.
View Article and Find Full Text PDFResearch Trends and Development Dynamics of qPCR-based Biomarkers: A Comprehensive Bibliometric Analysis.
Mol Biotechnol
January 2025
Chongqing Key Laboratory of Sichuan-Chongqing Co-Construction for Diagnosis and Treatment of Infectious Diseases Integrated Traditional Chinese and Western Medicine, College of Medical Technology, Chengdu University of Traditional Chinese Medicine, 1166 Liutai Avenue, Wenjiang District, Chengdu, 611137, Sichuan, China.
Quantitative polymerase chain reaction (qPCR) is a vital molecular technique for biomarker detection; however, its clinical application is impeded by the scarcity of robust biomarkers and the inherent limitations of the technology. This study conducted a bibliometric analysis of 4063 qPCR-based biomarker studies sourced from the Web of Science (WOS) database, employing VOSviewer and CiteSpace to generate multi-dimensional structural insights into this field. The results reveal a growing trend in research within this domain, with gene expression analysis playing a central role in the identification of potential biomarkers.
View Article and Find Full Text PDFDynamic characterization of circulating tumor DNA in HER2-altered advanced non-small cell lung cancer treated with pyrotinib and apatinib: Exploratory biomarker analysis from PATHER2 study.
Lung Cancer
December 2024
Department of Comprehensive Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. Electronic address:
Background: HER2 mutations are critical drivers of non-small cell lung cancer (NSCLC), affecting 2 %-3 % of patients and often leads to poor prognosis and limited response to conventional therapies. This study investigates the genomic characteristics and prognostic relevance of dynamic circulating tumor DNA (ctDNA) monitoring in advanced NSCLC patients with HER2 mutations treated with pyrotinib and apatinib.
Methods: The PATHER2 study included 33 advanced NSCLC patients harboring HER2 mutations or amplification, who received combination therapy of pyrotinib and apatinib.
Circulating tumour DNA in predicting and monitoring survival of patients with locally advanced rectal cancer undergoing multimodal treatment: long-term results from a prospective multicenter study.
EBioMedicine
January 2025
Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China. Electronic address:
Background: Neoadjuvant chemoradiotherapy (nCRT) is the standard for locally advanced rectal cancer (LARC). However, distant metastasis remains the primary cause of treatment failure. Early identification of high-risk individuals for personalized treatment may offer a solution.
View Article and Find Full Text PDFDynamic Changes in Circulating Tumor DNA During Immunotherapy for Head and Neck Cancer: SHIZUKU-HN Study.
Int J Mol Sci
December 2024
Department of Medical Oncology, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-Ku, Tokyo 113-8510, Japan.
Immune checkpoint inhibitors (ICIs) are effective in treating recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), but only 20% of patients achieve durable responses. This study evaluated circulating tumor DNA (ctDNA) as a real-time biomarker for monitoring treatment response in HNSCC. The SHIZUKU-HN study prospectively collected and analyzed serial plasma samples (n = 27) from HNSCC patients undergoing ICIs, using Guardant360 to assess ctDNA variant allele frequency (VAF) and genetic mutations.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!