High-dose furmonertinib in <i>EGFR</i> -mutated advanced NSCLC with brain metastases after EGFR-TKI resistance: The iFORCE phase II trial.

Abstract

8607 Background: Brain metastases (BM) are common in patients with EGFR -mutated ( EGFR m) non-small cell lung cancer (NSCLC) and are associated with poor prognosis. Furmonertinib is a pan- EGFR tyrosine kinase inhibitor (TKI) characterized by high central nervous system penetration and a wide therapeutic window. This study evaluated the efficacy and safety of high-dose furmonertinib (160 mg once daily) in previously EGFR-TKI-treated patients with EGFR m NSCLC and BM. Methods: iFORCE was a prospective, single-arm study conducted at a single center. Eligible patients had EGFR exon 19 deletion or L858R-mutant NSCLC with at least one measurable intracranial lesion (≥5 mm) and had received ≥1 prior EGFR-TKI therapy. Patients received furmonertinib 160 mg orally once daily. The primary endpoints were intracranial progression-free survival (iPFS). Results: Twenty-three patients were enrolled, with a median follow-up time of 19.7 months (95% confidence interval [CI], 14.5-25.3 months). Median iPFS was 14.6 months (95% CI, 4.2-not reached), with 12- and 24-month iPFS rates of 53.8% and 30.8%, respectively. The intracranial objective response rate (iORR) was 34.8% (95% CI, 16.4-57.3), and the intracranial disease control rate (iDCR) was 91.3% (95% CI, 72.0-98.9). Median systemic progression-free survival (PFS) was 10.7 months (95% CI, 3.9-not reached). Treatment-related adverse events occurred in 13 (56.5%) of patients and were predominantly grade 1; one patient (4.3%) experienced a grade 3 stomatitis. No treatment discontinuations or treatment-related deaths were observed. Conclusions: High-dose furmonertinib demonstrated encouraging intracranial efficacy with a manageable safety profile in previously EGFR-TKI-treated patients with EGFR m NSCLC and BM, supporting further investigation in randomized studies. Clinical trial information: NCT05465343 .