High-dose furmonertinib in combination with intraventricular chemotherapy for EGFR exon 20 insertion mutated lung adenocarcinoma with leptomeningeal metastasis.

e20555 Background: Leptomeningeal metastasis (LM) is a severe complication of advanced lung adenocarcinoma (LUAD) and always has a dismal prognosis. EGFR exon 20 insertion ( EGFR 20ins) is the third most common EGFR mutations; however, there are currently no reports focusing on LM with EGFR 20ins, and the optimal therapy for these patients remains unclear. This retrospective study aimed to evaluate the efficacy and safety of high-dose furmonertinib in combination with intraventricular chemotherapy in EGFR 20ins mutated LUAD patients with LM. Methods: Weretrospectively enrolled 10 LUAD patients with LM who had failed multiline treatment between May 2021 and June 2023 at Nanjing Chest Hospital. All of them had confirmed EGFR 20ins by next generation sequencing. All patients received furmonertinib in combination with intraventricular chemotherapy via the Ommaya reservoir. Furmonertinib was taken at 160 mg once daily. The chemotherapy regimen consisted of 30mg pemetrexed and 5 mg dexamethasone administered twice weekly for 2 weeks during the consolidation phase, followed by a maintenance phase every 3-4 weeks until disease progression or unacceptable toxicity, or patient refusal. Results: The median age was 53.5 years (range: 39-66), and six (60%) were males. Four patients (40%) had an ECOG of 3, and six patients (60%) had an ECOG of 4. The intracranial ORR (iORR) was 60% (6/10) and intracranial DCR (iDCR) was 90% (9/10). The ECOG PS improved in 80% patients after treatment. With a median follow-up of 9.3 months, the median intracranial progression-free survival (iPFS) was 7.3 months (95% CI, 3.3-NR) and the median overall survival (OS) was 8.8 months (95% CI, 4.9-NR), respectively. Treatment related adverse events of ≥ grade 3 occurred in only 2 patients, which were nausea and rash. Conclusions: Furmonertinib in combination with intraventricular chemotherapy is a tolerable treatment with breakthrough clinical efficacy for LUAD patients with LM harboring EGFR 20ins.