High-dose furmonertinib combined with bevacizumab and pemetrexed in non-small cell lung cancer patients with <i> <i>EGFR</i> </i> mutations and leptomeningeal metastasis: A prospective real-world study.

Abstract

8609 Background: Leptomeningeal metastasis (LM) in lung cancer is always associated with poor prognosis. Our previous study has demonstrated that high-dose furmonertinib offers promising efficacy in non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor( EGFR ) mutations and LM. In this study, we aim to further evaluate the efficacy and safety of high-dose furmonertinib combined with bevacizumab and pemetrexed in NSCLC patients with EGFR mutations and LM in the real world. Methods: Eligible patients had histologically or cytologically confirmed NSCLC harboring an EGFR mutation. Patients were diagnosed as LM according to the EANO-ESMO criteria. They were treated with high-dose furmonertinib (240 mg, daily), bevacizumab (15 mg/kg, every 3 weeks), and pemetrexed (50 mg, intrathecal chemotherapy or 500 mg/m², intravenous chemotherapy, every 3 weeks). The primary endpoint was overall survival (OS). Secondary endpoints included time to treatment failure (TTF), ORR-LM (objective response rate in leptomeningeal metastasis) according to the RANO-LM radiologic criteria, clinical response rate (assessed with improvement of neurologic symptoms or signs and changes in the performance status), and adverse events (AEs) (graded according to CTCAE v5.0). Results: Between March 10, 2023 and December 31, 2024, 33 patients were enrolled at Henan Cancer Hospital. 10 patients (30.3%) had EGFR exon 19 deletions, 18 patients (54.5%)had exon 21 L858R mutations, and the other 5 patients (15.2%) had non-classical mutations. 20 (60.6%) had an ECOG score of 1-2, while 13 (39.4%) had an ECOG score of 3. Additionally, 22 patients (66.7%) had received at least two prior lines of treatment, and 23 patients(69.7%) had previously been treated with third-generation EGFR-TKIs. 6 patients (18.2%) received pemetrexed via intravenous administration, while 27 patients (81.8%) received intrathecal chemotherapy of pemetrexed. The clinical response rate was 72.7%, the ORR-LM and disease control rate (DCR) assessed by investigator according to RANO-LM radiologic criteria were 64.7% and 94.1%.At the data cut off point of December 31, 2024, 7 (21.2%) patients had died. The median follow-up was 7.8 months. The median OS was not reached. 25 (75.8%) patients experienced treatment-related adverse events (TRAEs) of any grade. Grade 3 adverse events included: diarrhea (6.1%), leukopenia/neutropenia (9.1%), anemia (6.1%), and thrombocytopenia (3%). One patient experienced grade 4 leukopenia and thrombocytopenia. The dose of furmonertinib was reduced to 160mg in 4 patients and intrathecal chemotherapy was discontinued in one patient. Conclusions: High-dose furmonertinib combined with bevacizumab and pemetrexed demonstrates remarkable clinical efficacy and tolerable safety in NSCLC patients with EGFR mutations and LM. Clinical trial information: NCT06643000 .