Abstract 1050P
Background
Osimertinib is the new standard of care in epidermal growth factor receptor (EGFR)-mutated non-pretreated advanced non-small-cell lung cancer (NSCLC). The MELROSE study, a multicentric, open label, phase II trial (NCT03865511) was designed to identify resistance mechanisms at the time of disease progression in treatment-naive EGFR-mutated NSCLC patients receiving osimertinib. While these analyses are in progress, we explored secondary endpoints including ctDNA analysis.
Methods
The MELROSE trial enrolled 150 patients with treatment-naive EGFR-mutated (L858R or exon 19 deletion) NSCLC. All patients received osimertinib. Tumor assessment was performed every 3 months, with brain and thoracoabdominal CT-scan (RECIST 1.1). Blood was collected in Streck tubes at baseline (d0) and after 7 days of treatment (d7). Cell free DNA was extracted from plasma (3 mL) using the Maxwell RSC LV kit (Promega). EGFR mutations were quantified by digital PCR using a Naica system (Stilla Technologies), and the IDEGFR SENSI detection kit (IDSolutions).
Results
Data from 138 patients were analyzed (8 consents withdrawn and 4 patients with missing data). 81 patients (58.7%) presented an exon 19 deletion, and 57 (41.3%) an L858R mutation. Primary analysis (data cutoff on April 4, 2022) showed a median PFS of 19.6 months (1-year PFS: 69.8%). At baseline, 94 patients (68.1%) were found to contain ctDNA (detectable EGFR mutation) in plasma. The presence of ctDNA was associated with liver metastases (p<0.001). High baseline ctDNA concentrations were associated with worse PFS (p=0.001), and were an independent prognostic factor in multivariate analysis (p=0.014). PFS was correlated with the presence of ctDNA after 1 week on osimertinib (d7) (p=0.009; HR 1.971; 95% CI 1.187-3.272). Patients presenting a significant increase in ctDNA concentration between d0 and d7 had a greatly reduced PFS (3.3 months) as compared to patients with a significant decrease in ctDNA concentration at d7 (PFS=18.2 months) (p=0.002; HR 11.648; 95% CI 2.536-53.505).
Conclusions
PFS was independently associated with baseline ctDNA in NSCLC patients receiving first-line osimertinib. At day 7, an increase in ctDNA was associated with primary resistance.
Clinical trial identification
NCT03865511.
Editorial acknowledgement
Legal entity responsible for the study
Nantes University Hospital.
Funding
AstraZeneca.
Disclosure
All authors have declared no conflicts of interest.