EGFR-Mutated NSCLC: MRD Detection and Adjuvant Osimertinib

By: Vanessa A. Carter, BS
Posted: Tuesday, July 23, 2024

The ADAURA trial, conducted by Tom John, MD, of Peter MacCallum Cancer Centre, University of Melbourne, Australia, and colleagues, evaluated the use of the EGFR tyrosine kinase inhibitor osimertinib in patients with EGFR-mutated, stage IB to IIIA non–small cell lung cancer (NSCLC). The results of a molecular residual disease (MRD) analysis from this trial, which were presented during the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 8005), support the use of MRD detection to predict response to adjuvant osimertinib and disease recurrence in this patient population.

“MRD positivity preceded disease-free survival events in most patients, with a median lead time of 4.7 months across both arms,” the investigators mentioned. “MRD negativity was maintained for most patients during adjuvant osimertinib treatment, with the majority of MRD/disease-free survival events occurring after [treatment] completion.”

This phase III study enrolled 682 adults with completely resected, EGFR-mutated, stage IB, II, or IIIA NSCLC. Of the total, 220 circulating tumor DNA samples were evaluable for MRD; samples were collected at baseline, weeks 12 and 24, and then every 24 weeks for 5 years. Participants were randomly assigned on a 1:1 basis to receive 80 mg of once-daily osimertinib (n = 112) or placebo (n = 108) until treatment completion at 3 years, treatment discontinuation, or disease recurrence. 

The median follow-up among patients on osimertinib was twice as long as those on placebo (44.2 vs 19.1 months). Approximately 4% and 12% of individuals in the osimertinib and placebo arms were MRD-positive at baseline, respectively; four of five participants on osimertinib achieved MRD-negative status during treatment. MRD detection had a clinical sensitivity of 65%, as well as a specificity of 95%, among patients treated with osimertinib. The majority of participants in the osimertinib arm were MRD/disease-free survival event-free after 36 months; this was true for 36% of those in the placebo group. Of 28 patients who received osimertinib who experienced MRD/disease-free survival events, 19 did so after treatment.

Disclosure: For full disclosures of the study authors, visit coi.asco.org.

2024 ASCO Annual Meeting

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