Mefatinib as first-line treatment of patients with advanced non–small cell lung cancer harboring rare EGFR mutations.

Abstract

9102 Background: Mefatinib is a novel, second-generation, irreversible epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI). A Phase Ib/II study has showed promising efficacy in patients with advanced EGFR (19del/L858R) mutant non-small cell lung cancer (NSCLC). This study is aimed to assess the efficacy and safety of mefatinib as first-line therapy for advanced rare EGFR mutations (G719X/S768I/L861Q) NSCLC. Methods: In this phase II study, we enrolled patients with stage IIIB-IV lung adenocarcinoma with at least one mutation in G719X, L861Q, and S768I who hadn¡¯t received front-line anticancer therapy. Other concurrent EGFR mutations were allowed with the exception of Ex19del, L858R, and exon 20 insertions. Eligible patients were treated with mefatinib 80 mg orally once daily. The primary endpoint was objective response rate (ORR) according to RECIST 1.1 criteria. Results: A total of 21 patients (median age 57.6, 47.62% male) have been enrolled, 80.95% with G719X, 33.3% S768I, and 19.05% L861Q. Six (28.57%) patients had concurrent mutations of G719X and S768I, and one (4.76%) patient had co-mutations of G719X and L861Q. As of data cut-off (Jan, 6, 2022), median follow-up was 25.1 months. Among the 21 efficacy evaluable patients, ORR was 85.71% (95% CI, 63.66-96.95) with a duration of response (DOR) of 22.2 months (95% CI, 8.4-NA). Disease control rate (DCR) was 100% (95% CI, 83.89-100.00). Median progression-free survival (mPFS) was 20.6 months (95% CI, 8.3-NA). Median overall survival (OS) was not reached.. The most common treatment-related adverse events (TRAEs) were rash (20, 95.24%), diarrhea (19, 90.48%), stomatitis (15, 71.43%), and pandactilitis (9, 42.86%). Grade 3 TRAEs were reported in 47.63% patients. Common Grade 3 TRAEs (¡Ý5%) included diarrhea (8, 38.10%) and rash (5, 23.81%). No ¡ÝGrade 4 TRAE or treatment-related SAE reported. 33.33% (n=7) of patients experienced dose reduction due to AEs (mainly diarrhea and rash). All TRAEs were reversible and remained stable or recovered without sequelae after dose reduction. None of the patients discontinued treatment or died due to TRAE. Conclusions: Mefatinib has shown promising anti-tumor activity and a favorable safety profile in patients with advanced NSCLC harboring rare EGFR mutations. Clinical trial information: CTR20190110. [Table: see text]