Abstract 597P
Background
Adjuvant Osimertinib significantly improved survival in patients with resected EGFR-mutated stage IB-IIIA NSCLC (ADAURA). However, adjuvant EGFR-TKI treatment data for uncommon EGFR-mutated patients were lacking. The ADMIN study investigated the efficacy and safety of adjuvant Osimertinib in this setting and reported clinical characteristics, genomic profile, and plasma molecular residual disease (MRD).
Methods
This multicenter, single-arm study enrolled stage IB-IIIB NSCLC pts with uncommon EGFR mutations (G719X, S768I, L861Q or de novo T790M) received adjuvant Osimertinib (80 mg QD) after curative surgery. Adjuvant chemotherapy was allowed. The primary endpoint is 3-year DFS & secondary endpoints include 2/4/5-yr DFS, and 2/3/4/5-yr OS. Genomic profile was detected by whole exome sequencing (WES) in the resected tumor tissue. White blood cells and plasma from day one before adjuvant Osimertinib were used for MRD detection.
Results
29 pts were enrolled. 51.7% was female. Median age was 65 years, 37.9% with a smoking history. G719X in 11 pts (37.9%), L861Q in 10 pts (34.5%), G719X + S768I in 6 pts (20.7%) and G719X + L861Q in 2 pts (6.9%), G719 and L861 have a higher incidence among uncommon mutations, which is consistent with previous studies. None of pts showed de novo T790M mutations. 14 pts (48.3%) were stage IB, 5 pts 17.2%) were stage II and 10 pts (34.4%) were stage IIIA-IIIB. 72.4% pts (21/29) were L861Q or G719X mutation, 27.6% pts (8/29) were G719x+S768I/L861Q. Plasma ctDNA test showed that 27.6% (8/29) pts were MRD positive. Most of them were male (5 pts, 62.5 %), age < 65 (5 pts, 62.5 %), in T2 (5pts, 62.5%), lymph status of N2 (6 pts, 75%) and stage IIIA (6 pts, 75%). In MRD-positive pts, 4 pts (50%) with smoking history and 4 pts (50%) with L861Q. Overall, MRD status was significantly associated with primary tumor size (p=0.022), lymph node metastasis (late N stage, p=0.005), and stage (late stage, p=0.002).
Conclusions
This analysis reported the genomic profile and MRD status of 29 pts in uncommon EGFR mutation stage IB-IIIB resected NSCLC. MRD-positive patients have significantly larger primary tumor, more lymph node metastasis or in a later stage.
Clinical trial identification
NCT05546866.
Editorial acknowledgement
The authors thank Dr. Ravi Kiran Ammu, PhD and Dr. Deepak Pakalapati, PhD from Indegene Private Limited, India for their editorial and writing assistance.
Legal entity responsible for the study
AstraZeneca, China is the legal entity responsible for the study.
Funding
AstraZeneca, China.
Disclosure
W. Huang, J. Wang: Financial Interests, Institutional, Affiliate, Employee: AstraZeneca. All other authors have declared no conflicts of interest.