At the San Antonio Breast Cancer Symposium (SABCS) 2024, Dr. Nicholas Turner presented findings from the ZEST trial, which explored the use of circulating tumor DNA (ctDNA) for detecting molecular residual disease (MRD) in breast cancer patients. Here’s an overview of the study:
Study Overview:
- Aim: The ZEST trial investigated whether the PARP inhibitor Niraparib could enhance disease-free survival in patients with detectable ctDNA after standard therapy but no clinical signs of recurrence.
- Participants: Included were patients with stage 1-3 breast cancer, specifically those with triple-negative or hormone receptor-positive cancers with BRCA mutations. All had finished curative intent treatments and were on ctDNA surveillance.
- Method: The Signatera assay was used for bi-monthly ctDNA monitoring. Patients with ctDNA but no clinical recurrence were randomized to receive either Niraparib or placebo, divided into BRCA mutation and BRCA wild-type TNBC cohorts.
Key Findings:
- ctDNA Detection: Only 8% of the 1,900 patients monitored had detectable ctDNA, indicating the inclusion of a broader, lower-risk patient population.
- Recurrence Prediction: The study confirmed ctDNA’s ability to predict recurrence with high sensitivity, although half of the ctDNA-positive patients already had radiologic signs of recurrence.
- Trial Limitations: The trial managed to randomize only 40 patients out of the intended 800 due to high immediate recurrence rates and other exclusion criteria.
- Outcome Measures: The limited data suggested a slight increase in median recurrence-free interval with Niraparib, but the study wasn’t adequately powered to make definitive conclusions on efficacy.
Challenges Identified:
- Disease Dynamics: In TNBC, the rapid transition from ctDNA detection to clinical recurrence suggests that the window for intervention might be narrow with current technologies.
- Assay Performance: There’s an ongoing need for assays with greater sensitivity to detect ctDNA earlier, particularly in aggressive cancers.
- Patient Involvement: The consent process was relatively straightforward, but the inclusion of lower-risk patients highlighted challenges in trial design for ctDNA studies.
Clinical Considerations:
- Practical Use: Dr. Turner advised caution in adopting ctDNA testing clinically until there are clear treatment protocols post-detection, to avoid unnecessary patient anxiety.
- Research Directions: The study points to the necessity for more research to better tailor ctDNA detection to patient management, especially in cancers with different progression rates.
Conclusion:
The ZEST trial provides valuable insights into the challenges of implementing ctDNA surveillance in breast cancer management. It emphasizes the importance of integrating detection methods with effective therapeutic strategies to improve patient outcomes without causing undue distress. Further commentary and expert opinions from SABCS 2024 can offer additional perspectives on these findings.