Efficacy and safety of furmonertinib in patients with EGFR‑mutant advanced lung adenocarcinoma after failure of multiple lines of therapy: A single‑center retrospective study

Abstract

Currently, treatments for patients with non-small cell lung cancer harboring epidermal growth factor receptor (EGFR) mutations are limited after receiving multiple lines of therapy. Furmonertinib, a newly developed third-generation EGFR-tyrosine kinase inhibitor (TKI), has shown potential as a subsequent treatment. To explore efficacy and safety of furmonertinib, the present retrospective study analyzed patients with EGFR-mutant advanced lung adenocarcinoma (LUAD) who received furmonertinib after the failure of multiple lines of therapy at the China-Japan Friendship Hospital (Beijing, China) between December 2021 and April 2024. Data on patient demographics, treatment efficacy and safety outcomes were assessed until disease progression. A total of 25 patients with advanced LUAD were retrospectively included in the analysis. Among them, 15 (60.0%) harbored exon 19del, whilst 10 (40.0%) had exon21 L858R mutations. Pre-treatment genetic testing was performed in 14 patients (56.0%). Prior to furmonertinib therapy, 17, 5 and 19 patients had previously received first-, second- and third-generation EGFR-TKIs, respectively. The median line of treatment before furmonertinib was 3. The median progression-free survival was 5.73 (95% confidence interval, 4.30-not reached) months. The objective response rate was 16.0% (n=4) and the disease control rate was 88.0% (n=22). A total of 18 (72.0%) patients experienced at least one adverse event (AE). The rate of AEs was 80.0% (n=20) for grade 1-2, and 20.0% (n=5) for grade 3-4 AEs. No AEs led to treatment discontinuation, dose reductions or death. In conclusion, furmonertinib is a viable treatment option for patients with EGFR-mutant advanced LUAD after the failure of multiple lines of therapy, even after resistance to treatment with third-generation EGFR-TKIs targeted agents. However, further large-scale clinical studies are warranted to validate these findings.

Keywords: epidermal growth factor receptor-tyrosine kinase inhibitors; furmonertinib; lung adenocarcinoma; multiple lines of therapy; targeted therapies.

Figure 1.

Sunburst of previous epidermal growth factor receptor-tyrosine kinase inhibitor treatments received before furmonertinib. The inner to outer circles represent the first, second and third generations of EGFR-TKIs. The numbers refer to the number of patients who received EGFR-TKI. No, the patient did not receive the corresponding EGFR-TKIs. EGFR, epidermal growth factor receptor; TKI, tyrosine kinase inhibitor.

Figure 2.

Kaplan-Meier survival curves of mPFS in patients who received furmonertinib. mPFS of (A) 25 patients with EGFR mutated lung adenomcarcinoma after the failure of multiple lines of therapy; (B) 19 patients who were previously resistant to third-generation EGFR-tyrosine kinase inhibitor-targeted agents; and (C) 17 patients who had previously received treatment with osimertinib. mPFS, median progression-free survival; EGFR, epidermal growth factor receptor; CI, confidence interval; NR, not reached.

Figure 3.

Forest plot of subgroup analysis for progression-free survival in 25 patients who received furmonertinib. CI, confidence interval; EGFR, epidermal growth factor receptor; TKI, tyrosine kinase inhibitor.

Figure 4.

Kaplan-Meier survival curves of the mPFS of patients who received furmonertinib. (A) Metastases localized in the chest; (B) Disease progression with BM or OM; (C) EGFR mutation status; and (D) Dosage of furmonertinib. mPFS, median progression-free survival; EGFR, epidermal growth factor receptor; NR, not reached; BM, brain metastases; OM, other metastases.