Objective: To investigate the impact of SMARCA4 mutations on the outcomes of patients with advanced lung adenocarcinoma with epidermal growth factor receptor (EGFR) mutations. Methods: In the Memorial Sloan Kettering Cancer Center (MSK) MetTropism study, 960 patients with advanced EGFR-mutated lung adenocarcinoma were screened and included in the MSK cohort, composing of 313 males and 647 females, with a median [M(Q1, Q3)] age of 64 (56, 72) years. A retrospective analysis was conducted on the data of 178 patients with advanced EGFR-mutated lung adenocarcinoma who received EGFR tyrosine kinase inhibitors (TKIs) treatment in the Department of Oncology, the First Affiliated Hospital of Nanjing Medical University, from January 2018 to December 2022. Among these patients, 69 were males and 109 were females, with a median age of 63 (54, 69) years. The follow-up of patients from the First Affiliated Hospital of Nanjing Medical University was conducted up to December 31, 2023, with a median follow-up time of 26.6 (95%CI: 24.6-28.6) months for the entire cohort, and 29 patients were lost to follow-up. Survival curves were plotted using the Kaplan-Meier method, and the log-rank test was used to compare the relationship between SMARCA4 gene alternations and prognosis. Results: In the 960 patients of the MSK cohort with advanced EGFR-mutated lung adenocarcinoma, the SMARCA4 gene alternations rate was 4.2% (40/960). The median overall survival (OS) for patients without SMARCA4 gene alternations was 41.5 (95%CI: 35.6-47.3) months, which was superior to that of patients with SMARCA4 gene alternations [15.6 (95%CI: 7.9-23.4) months, P<0.001]. Patients with SMARCA4 gene alternations had a higher risk of mortality, with an HR (95%CI) of 1.97 (1.35 to 2.88). Among the 178 patients with advanced EGFR-mutated lung adenocarcinoma from the First Affiliated Hospital of Nanjing Medical University, the SMARCA4 gene alternations rate was 4.5% (8/178). The median progression-free survival (PFS) for patients without SMARCA4 gene alternations was 16.1 (95%CI: 12.2-20.0) months, which was superior to the median PFS of patients with SMARCA4 gene alternations [6.0 (95%CI: 1.3-10.7) months, P<0.001]. The median OS for patients without SMARCA4 gene alternations was 50.1 (95%CI: 28.1-72.1) months, which was also superior to the median OS of patients with SMARCA4 gene alternations [17.6 (95%CI: 15.4-19.8) months, P=0.001]. Conclusion: SMARCA4 alternation is an important factor associated with poor prognosis in patients with advanced EGFR-mutant lung adenocarcinoma.
目的： 探讨SMARCA4基因变异对晚期表皮生长因子受体（EGFR）突变肺腺癌患者预后的影响。 方法： 在斯隆-凯特林（MSK）MetTropism研究中筛选960例EGFR突变晚期肺腺癌患者作为MSK队列，其中男313例，女647例；年龄［M（Q1，Q3）］为64（56，72）岁。回顾性分析2018年1月至2022年12月在南京医科大学第一附属医院肿瘤科接受EGFR酪氨酸激酶抑制剂（TKIs）治疗的178例晚期EGFR突变肺腺癌患者资料，其中男69例，女109例；年龄为63（54，69）岁；随访截至2023年12月31日，中位随访时间为26.6（95%CI：24.6~28.6）个月，失访29例。以Kaplan-Meier法绘制生存曲线，采用log-rank检验进行MSK队列中不同特征晚期EGFR突变肺腺癌患者生存时间比较，多因素Cox回归模型分析生存结局的影响因素。 结果： MSK队列SMARCA4基因变异率为4.2%（40/960）；无SMARCA4基因变异患者的中位生存时间（OS）为41.5（95%CI：35.6~47.3）个月，优于SMARCA4基因变异患者［15.6（95%CI：7.9~23.4）个月，P<0.001］；SMARCA4基因变异患者死亡风险较高，HR（95%CI）为1.97（1.35~2.88）。南京医科大学第一附属医院队列SMARCA4基因变异率为4.5%（8/178）。无SMARCA4基因变异患者的中位无进展生存时间（PFS）为16.1（95%CI：12.2~20.0）个月，优于SMARCA4基因变异患者［6.0（95%CI：1.3~10.7）个月，P<0.001］；无SMARCA4基因变异患者中位OS为50.1（95%CI：28.1~72.1）个月，优于SMARCA4基因变异患者［17.6（95%CI：15.4~19.8）个月，P=0.001］。 结论： SMARCA4基因变异是晚期EGFR突变肺腺癌患者预后不良的重要影响因素。.