The ADAURA trial findings showed a significant benefit in disease-free survival with the EGFR inhibitor osimertinib, compared to placebo, making it the recommended standard of adjuvant treatment in patients with EGFR-mutated non–small cell lung cancer (NSCLC) for up to 3 years after surgery.
In a study published recently in Nature Medicine, Herbst et al followed patients from the ADAURA study to evaluate whether detection of circulating tumor DNA–based molecular residual disease (MRD) after primary treatment was predictive of recurrence.
“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 Roy Herbst, MD, Deputy Director of Yale Cancer Center and Chief of Medical Oncology and Hematology at Yale School of Medicine. “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.” Dr. Herbst is also the Assistant Dean for Translational Research at Yale School of Medicine.
The exploratory post hoc analysis included 220 patients (n = 112 osimertinib; n = 108 placebo) from ADAURA. At randomization to adjuvant osimertinib vs placebo, the number of patients with MRD detected was small, but it seemed to be associated with poor outcomes for both the osimertinib and placebo groups.
The researchers reported that if MRD proves valid for clinical purposes it could improve outcomes by identifying high-risk patients who might benefit from intensifying or restarting adjuvant osimertinib treatment. Conversely, MRD could also identify patients with low risk of recurrence, possibly sparing them from further treatment and any associated drug toxicities as a result.
“MRD detection is the future—allowing us to monitor patients in real-time,” said Dr. Herbst. “The data [are] strong and we're excited that our approach can now be incorporated into future studies.”
Dr. Herbst and Yi-Long Wu, MD, of the Guangdong Lung Cancer Institute, were co–corresponding authors for the Nature Medicine article.
Disclosure: This research was supported by AstraZeneca. For full disclosures of all study authors, visit nature.com.
