ADAURA Trial Shows How MRD May Predict Benefit of Adjuvant Therapy in EGFR-Positive NSCLC

The detection of molecular residual disease (MRD) in patients with EGFR-positive non-small cell lung cancer (NSCLC) may determine if they’ll benefit from longer adjuvant therapy, according to a study presented at the 2024 American Society of Clinical Oncology Annual Meeting.

Researchers from the phase 3 ADAURA clinical trial, which investigated osimertinib for disease-free survival (DFS) and overall survival (OS), examined MRD and its helpfulness in predicting disease recurrence.

“Adjuvant osimertinib (3 years) is recommended for resected EGFR mutant stage IB–IIIA NSCLC based on significant improvements in DFS and OS. A trend towards an increased DFS event rate beyond 3 years suggests some patients may benefit from longer adjuvant osimertinib treatment,” the researchers said.

Patients (n=682) were randomly selected to either receive osimertinib 80 mg once a day or placebo until disease recurrence, treatment completion, or discontinuation.

Those enrolled in the study were at least 18 years old, had completely resected EGFR-mutated stage 1B-IIIA NSCLC, and a World Health Organization performance status of 0 or 1.

Plasma sample collections took place at baseline, every 12 weeks during treatment, then at treatment discontinuation, and after treatment completion (week 12, week 24, then every 24 weeks until 5 years).

Across both groups, 32% (n=220) of participants who produced MRD panels were evaluated. At baseline, 4% (n=5/112) of patients in the osimertinib group were MRD positive compared with 12% (n=13/108) in the placebo group. Moreover, during treatment, 4 of the 5 patients who received osimertinib became MRD negative. None of the patients who received placebo reached MRD negativity.

On treatment, MRD detection had a clinical sensitivity of 65% (62 MRD positive/96 DFS positive), a specificity of 95% (118 MRD negative/124 DFS negative) and preceded a DFS event by a median of 4.7 months across the 2 groups.

At 36 months, 86% of patients in the osimertinib group, compared with 36% in the placebo group were MRD/DFS event-free.

“MRD negativity was maintained for most patients during adjuvant osimertinib treatment with the majority of MRD/DFS events occurring after osimertinib treatment completion,” the researchers said.

Reference

John T, Grohe C, Goldman JW, et al. Molecular residual disease (MRD) analysis from the ADAURA trial of adjuvant (adj) osimertinib in patients (pts) with resected EGFR‑mutated (EGFRm) stage IB–IIIA non-small cell lung cancer (NSCLC). Abstract #8005. Presented at the 2024 American Society of Clinical Oncology Annual Meeting; May 31-June 4, 2024, Chicago, Illinois.