Dr Lee on the Optimal Duration of Adjuvant Osimertinib in EGFR+ NSCLC

“What we do know is that ctDNA detection is one way to follow patients, and it’s certainly prognostic for clinical relapse, and depending on what study you look at, it’s around a six-month lead time before a relapse occurs clinically.”

Jay M. Lee, MD, surgical director of the Thoracic Oncology Program, and professor of surgery at the David Geffen School of Medicine at UCLA, discussed the role of circulating tumor DNA (ctDNA) in guiding surveillance and treatment escalation decisions in resected non–small cell lung cancer (NSCLC), a topic covered in the Bridging the Gaps in Lung Cancer meeting.

Lee explained that ctDNA detection is a validated method for longitudinal patient surveillance and is prognostic for clinical relapse, typically providing a lead time of approximately 6 months before relapse becomes clinically apparent, depending on the study. This raises the question of whether detecting minimal residual disease (MRD) through longitudinal ctDNA surveillance should serve as a basis for escalating therapy in patients who otherwise appear to have no evidence of disease.

Lee noted that ctDNA-positive, radiographically disease-free patients could potentially be managed with continued surveillance, reinitiation of therapy if previously stopped, or treated similarly to stage IV patients given their significant relapse risk. He said future trials will need to determine whether this population truly requires escalated therapy, particularly for patients remaining on osimertinib (Tagrisso) with persistently detectable ctDNA that fails to clear, which may signal the presence of resistant cells.

Lee raised the possibility of a response-adaptive trial design that would escalate treatment using next-generation, fourth-generation EGFR TKIs currently in early development, or combination strategies already being explored in the metastatic setting.