Abstract 54P
Background
We observed that leptomeningeal metastases (LM) occurred more offen in patients resistant to third-generation EGFR-TKIs, while these patients lacked of effective therapy. In a retrospective study, firmonertinib (furmonertinib) 160 mg combined with intrathecal injection methotrexate (MTX) or pemetrexed (PEM) has been demonstrated encouraging efficacy in NSCLC patients with EGFR mutations and LM. Here we report the cohort 4 of the prospective study (ChiCTR2300071395), aimed to evaluate the efficacy and safety of patients with EGFR mutations and LM who received high dose firmonertinib combined with intrathecal injection pemetrexed (PEM).
Methods
Patients confirmed advanced NSCLC with EGFR mutations and LM received firmonertinib 160 mg, qd, combined with intrathecal injection PEM 40 mg, q3w, until disease progression or unacceptable toxicity. The primary endpoint was median intracranial progression-free survival, and secondary endpoints were PFS, LM response rate according to RANO criteria, median overall survival (OS) and safety.
Results
This cohort included totally 57 advanced NSCLC patients with EGFR mutations and LM diagnosed by CSF cytology at Beijing Tiantan Hospital between April 2023 and November 2024 and forty cases were included in this analysis. The median age was 60.5 years (range: 38–72), ECOG PS≥2 52.5%, 80% patients had received systemic therapy, and 65% patients had received third-generation EGFR-TKIs previously, all patients were adenocarcinoma. The median follow-up time was 9.2 months (range: 2–19.6), the median intracranial PFS was not reached, the median PFS was 10.2 months (95%CI 7.93–12.30). LM response was observed in 5 (14%) of 36 patients, LM response and stable diseases were observed in 32 (89%) of 36 patients according to RANO-LM. the median OS was 15.4 months (95%CI 10.41–20.39). The incidence of treatment-related adverse events (TRAEs) were 67.5%, grade 3 or higher TRAEs were occurred in 2 (5%) patients. The most common TRAEs were diarrhea (17.5%) and rash (15%).
Conclusions
Firmonertinib 160 mg combined with intrathecal injection pemetrexed showed encouraging efficacy in NSCLC patients with EGFR mutations and LM.
Clinical trial identification
ChiCTR2300071395, May 15, 2023.
Legal entity responsible for the study
Ethics Committee of Beijing Tiantan Hospital.
Funding
Beijing Natural Science Foundation (NO. 7242007) and Beijing Xisike Clinical Oncology Research Foundation (Y-2021AST/zd-0127).
Disclosure
All authors have declared no conflicts of interest.