Objective To investigate the effect of BIM deletion polymorphism on the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in the treatment of EGFR19/21 mutant lung adenocarcinoma.

Methods A total of 98 patients with inoperable or advanced lung adenocarcinoma with EGFR19/21 mutations were selected, and divided into two groups based on gene testing results: 32 patients with both BIM deletion polymorphism and EGFR19/21 co-mutations (co-mutation group) and 66 patients with EGFR19/21 single mutations (single mutation group). All patients received EGFR-TKIs (first-generation icotinib/gefitinib or third-generation osimertinib) treatment. After 6 weeks of oral treatment, the efficacy was evaluated, and the best response was recorded. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were compared between the two groups. Kaplan-Meier method was used for survival analysis, and multivariable Cox regression model was employed to analyze the factors influencing PFS and OS.

Results The ORR in the co-mutation group and the single-mutation group was 43.8% (14/32) and 80.3% (53/66), respectively, and the DCR in the co-mutation group and the single-mutation group was 71.9% (23/32) and 92.4% (61/66), respectively. The ORR and DCR in the co-mutation group were obviously lower than those in the single-mutation group (P ＜ 0.01). The median PFS in the co-mutation group and the single-mutation group was 6.80 months (95% CI: 1.81–11.79) and 11.30 months (95% CI: 9.06–13.54), respectively, and the median OS was 23.80 (95% CI: 18.40–29.21) and 31.50 (95% CI: 29.08–33.92), respectively. The median PFS and median OS in the co-mutation group were lower than those in the single-mutation group (P ＜ 0.05). Cox regression analysis revealed that EGFR-TKI type (first-generation or third-generation) and BIM deletion polymorphism were independent risk factors for PFS in patients treated with EGFR-TKIs (P ＜ 0.05 and P ＜ 0.01), while brain metastasis and BIM deletion polymorphism were independent risk factors for OS in patients treated with EGFR-TKIs (P ＜ 0.05 and P ＜ 0.01).

Conclusions BIM deletion polymorphism can reduce the efficacy of EGFR-TKIs in first-line treatment of EGFR19/21 mutant lung adenocarcinoma, and is an independent adverse prognostic factor for EGFR-TKIs in the treatment EGFR19/21 mutant lung adenocarcinoma patients.