1346P - Efficacy and safety of high dose furmonertinib combined with intrathecal injection in EGFR-mutated advanced NSCLC patients with LM progressed on osimertinib

Background

We observed that leptomeningeal metastases (LM) occurred more in patients with site-specific resistant to osimertinib than first-generation EGFR-TKI, while these patients lacked of effective therapy. Furmonertinib 160 mg has been demonstrated encouraging efficacy in EGFR-mutated advanced NSCLC with central nervous system (CNS) metastases. This retrospective study aimed to evaluate the efficacy and safety of high dose furmonertinib combined with intrathecal injection methotrexate (MTX) or pemetrexed (PEM) in EGFR-mutated NSCLC patients with LM site-specific resistance to osimertinib.

Methods

Patients confirmed EGFR-mutated advanced NSCLC with LM progressed on osimertinib or other third-generation TKIreceived furmonertinib 160 mg or 240 mg combined with intrathecal injection MTX or PEM until disease progression. The primary endpoint was central nervous system progression-free survival (CNS PFS), and secondary endpoints were LM response rate according to RANO criteria, PFS, overall survival (OS) and safety.

Results

This retrospective study analysed the efficacy and safety of 23 EGFR-mutated advanced NSCLC patients with LM at Beijing Tiantan Hospital between June 2021 and April 2023. The median age was 63 years (range: 41-78) , ECOG PS≥2 65.2%, 82.6% patients had received other third-generation EGFR-TKI previously, all patients were adenocarcinoma. The median follow-up time was 8.2 months (range: 0.9-14.1), the median CNS PFS was 10.8 months, LM response was observed in 6 (31.6%) of 19 patients with available data. The median PFS was 10.8 months, the median OS was NR. The CSF tumors cells decreased from baseline was observed in 14 (73.7%) of 19 patients with available data, and the CSF tumor cells clearance was observed in 6 (31.6%) patients. Neurologic function was improved in 18 (90.0%) of 20 patients. The most common treatment-related adverse events (TRAEs) were dry skin (17.4%) and elevated AST/ALT (17.4%). Nograde 3 or higher TRAEs observed.

Conclusions

High dose furmonertinib combined with intrathecal injection showed encouraging efficacy in EGFR-mutated advanced NSCLC patients progressed on osimertinib or other third-generation TKI.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

This study was supported by the grants from National Natural Science Foundation of China (NO.81974361), Beijing Xisike Clinical Oncology Research Foundation (Y-2021AST/zd-0127) and Beijing Municipal Education Commission-Beijing Natural Science Foundation Union Program (KZ202010025046).

Disclosure

All authors have declared no conflicts of interest.