584P - Upfront aumolertinib for preventing symptomatic central nervous system(CNS) metastases in EGFR-mutant non-small cell lung cancer without baseline CNS metastasis

Background

CNS metastases are associated with high clinical burden and mortality risk in patients with advanced EGFR+ NSCLC. The phase III AENEAS study showed that aumolertinib, a novel third-generation EGFR-TKI, significantly improved median CNS PFS in comparison to gefitinib in treatment-naive EGFR+ NSCLC patients with CNS metastases (29.0 vs 8.3months, hazard ratios: 0.319). In this study, we explore whether aumolertinib could potentially delay or prevent symptomatic CNS metastases in EGFR+ NSCLC patients without baseline CNS metastasis.

Methods

We included all consecutive EGFR+ NSCLC patients who underwent first or second-line aumolertinib treatment without baseline CNS metastasis (April 2021 to February 2023). We estimated the cumulative incidence of subsequent symptomatic CNS metastases, CNS median PFS, and their associated risk factors using the Kaplan–Meier method and the log-rank test. Images obtained upon EGFR-TKI initiation and at the time of EGFR-TKI treatment failure. Follow-up brain scans were not mandatory, typically after the appearance of indicative symptoms. Supplementary follow-up telephone interviews were also employed.

Results

A total of 88 pts were enrolled. At data cutoff,the median follow-up was 21 months,with only 1 pt experienced symptomatic CNS metastases. The cumulative incidence of symptomatic CNS metastasis at 12, 18, and 24 months were 0%, 1.538%, and 1.538%, respectively.For the 62 pts who received second-line aumolertinib,the cumulative incidence of symptomatic CNS metastases at the same time points was 0%. However, the cumulative incidence curves of symptomatic CNS metastasis tended to reach a plateau after approximately 18 months.The cumulative incidence with aumolertinib was lower than historical data from first-generation EGFR-TKIs and also demonstrated a declining trend compared to historical data from the retrospective study of Osimertinib (1-2% at 12 months; 2-3% at 24 months; 11.8% at 36 months).

Conclusions

This is the first study to demonstrate that Aumolertinib can reduce the risk of symptomatic CNS metastasis in EGFR+ NSCLC patients without baseline CNS metastasis.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.