A new blood test designed to monitor minimal residual disease (MRD) in patients with non-small cell lung cancer (NSCLC) is showing promise in improving clinical outcomes. The findings, published in Nature Medicine, were based on data from the ADAURA clinical trial evaluating the tyrosine kinase inhibitor (TKI) drug osimertinib for treatment of NSCLC in patients with epidermal growth factor receptor (EGFR)-activated mutations.
“MRD detection is the future—allowing us to monitor patients in real-time,” said first author Roy Herbst, MD, PhD, deputy director of Yale Cancer Center, and chief of medical oncology and hematology at Yale School of Medicine. “The data is strong and we’re excited that our approach can now be incorporated into future studies.”
The treatment monitoring protocol detailed in the study provides a compelling case for using MRD testing in the ongoing care of patients who have undergone treatment for stage IB–IIIA EGFR-mutated NSCLC. The study was conducted with patients from the ADAURA clinical trial, which previously established the efficacy of osimertinib—a third-generation EGFR-TKI—as an adjuvant therapy for resected EGFR-mutated NSCLC.
In the trial, osimertinib was shown to significantly improve disease-free survival (DFS) as a post-surgery adjuvant therapy compared to placebo. While the treatment offers extended survival, researchers wanted to better understand how effective treatment was and to determine which patients risked recurrence. MRD can provide this kind of information to treating physicians.
“We know patients benefited from osimertinib in the ADAURA trial, but we want to know if they are cured or whether their cancer will come back,” said Herbst. “MRD detection is a more personalized approach for patients with EGFR mutations in the adjuvant setting and now we’re understanding at what point patients start to benefit and how we can more precisely target their therapy.”
Oncologists are increasingly turning to liquid biopsy-based MRD testing for a range of cancer patients to monitor both treatment efficacy and to potentially get a head start on treating cancer recurrence. Using a blood test can often uncover evidence of disease recurrence moths before traditional imaging methods. In this study, MRD detection preceded clinical recurrence by an average of 4.7 months in patients who had completed treatment, offering a crucial lead time for clinicians.
“We believe MRD detection could identify high-risk patients who might benefit from restarting or intensifying treatment, and similarly, it could also identify low-risk patients who may avoid unnecessary therapy and its associated toxicities,” Herbst noted.
The results of this study also demonstrate that MRD testing could potentially extend the treatment window for patients who are at higher risk of recurrence. “In this study, MRD preceded DFS (disease-free survival) events in most patients across both arms,” the researchers wrote. “DFS and MRD event-free status were maintained for most patients during adjuvant osimertinib treatment and posttreatment follow-up.”
While the findings show the positive potential of using MRD to get a jump on treating recurrent cancers, it can also play an important role in determining when to stop treating patients who have responded.
“This analysis supports the idea that patients who do not show detectable MRD may be disease-free, eliminating the need for further treatment,” the researchers wrote. “However, the test also allows for more intensive care for those who are at risk of relapse, making it a highly sensitive tool for personalized medicine.”
While the study represents one of the largest studies of its kind in resected EGFR-mutated NSCLC, the researchers acknowledged that more work is needed. The next steps for their work include exploring how MRD can predict optimal treatment durations for individual patients.
