A real-world study of the efficacy and safety of furmonertinib for patients with non-small cell lung cancer with EGFR exon 20 insertion mutations

Background Furmonertinib is a novel third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). A phase Ib study (FAVOUR, NCT04858958) initially demonstrated the efficacy of furmonertinib in non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion (ex20ins). This study aimed to investigate the real-world efficacy and safety of furmonertinib in patients with advanced NSCLC with EGFR ex20ins. Methods We retrospectively examined patients with advanced NSCLC with EGFR ex20ins having complete follow-up data, who were treated with furmonertinib from April 14, 2021, to March 15, 2022, at our institution and multiple hospitals in China. Objective response rate (ORR), disease control rate (DCR), 6-month progression-free survival (PFS) rates and treatment related adverse events (TRAEs) were assessed. Results This study included 53 patients with advanced NSCLC with EGFR ex20ins. A767_V769dup (28.3%) and S768_ D770dup ( 11.3%) are the major variants. The ORR and DCR were 37.7% (20/53) and 92.5% (49/53), respectively. The 6-month PFS rate was 69.4% (95% CI 53.7-85.1%). The ORR of patients in the 240 mg once-daily dosage group was higher (42.9%) than that of patients in the 80 mg once-daily (25.0%) and 160 mg once-daily (39.5%) groups, but with no statistically significant difference (P = 0.816). The ORR of furmonertinib is not dependent on insertion location (P = 0.893). Patients with central nervous system (CNS) metastases at baseline responded similarly to those without CNS metastases (ORR: 33.3% vs. 40.6%, P = 0.773). The most common AEs were diarrhea (26.4%) and rash (26.4%). No grade >= 3 TRAEs were observed. No statistically significant difference was observed in the incidence of TRAEs between dosage groups (P = 0.271). Conclusions Furmonertinib has shown encouraging antitumor activity and CNS activity in patients with advanced NSCLC with EGFR ex20ins. Moreover, furmonertinib had a good safety profile and no dose-dependent toxicity.