背景:伴随表皮生长因子受体(EGFR)和TP53突变的非小细胞癌(NSCLC)患者接受酪氨酸激酶抑制剂(TKIs)治疗后预后不良,并且可以优先受益于组合方案。本研究旨在比较EGFR-TKIs及其与抗血管生成药物或化疗的联合应用在现实环境中EGFR和TP53共突变的NSCLC患者中的益处。
方法:这项回顾性分析包括124例伴有EGFR和TP53突变的晚期NSCLC患者,谁在治疗前接受了下一代测序。将患者分为EGFR-TKI组和联合治疗组。这项研究的主要终点是无进展生存期(PFS)。绘制Kaplan-Meier(KM)曲线分析PFS,并使用对数秩检验比较各组之间的差异。对与生存相关的危险因素进行单因素和多因素cox回归分析。
结果:联合治疗组包括72例接受EGFR-TKIs联合抗血管生成药物或化疗的患者,而EGFR-TKI单药治疗组包括52例仅接受TKI治疗的患者.组合组的中位PFS明显长于EGFR-TKI组(18.0个月;95%置信区间[CI]:12.1-23.9vs.7.0个月;95%CI:6.1-7.9;p<0.001)在TP53外显子4或7突变亚组具有更大的PFS益处。亚组分析显示出类似的趋势。联合组的中位反应持续时间明显长于EGFR-TKI组。与单独使用EGFR-TKI相比,具有19个缺失或L858R突变的患者联合治疗均获得了显着的PFS益处。
结论:联合治疗对同时存在EGFR和TP53突变的NSCLC患者的疗效优于单独使用EGFR-TKI。需要未来的前瞻性临床试验来确定联合治疗对该患者人群的作用。
BACKGROUND: Non-small cell cancer (NSCLC) patients with concomitant epidermal growth factor receptor (EGFR) and TP53 mutations have a poor prognosis with the treatment of tyrosine kinase inhibitors (TKIs), and may benefit from a combination regimen preferentially. The present
study aims to compare the benefits of EGFR-TKIs and its combination with antiangiogenic drugs or chemotherapy in patients with NSCLC harboring EGFR and TP53 co-mutation in a real-life setting.
METHODS: This retrospective analysis included 124 patients with advanced NSCLC having concomitant EGFR and TP53 mutations, who underwent next-generation sequencing prior to treatment. Patients were classified into the EGFR-TKI group and combination therapy group. The primary end point of this
study was progression-free survival (PFS). The Kaplan-Meier (KM) curve was drawn to analyze PFS, and the differences between the groups were compared using the logarithmic rank test. Univariate and multivariate cox regression analysis was performed on the risk factors associated with survival.
RESULTS: The combination group included 72 patients who received the regimen of EGFR-TKIs combined with antiangiogenic drugs or chemotherapy, while the EGFR-TKI monotherapy group included 52 patients treated with TKI only. The median PFS was significantly longer in the combination group than in the EGFR-TKI group (18.0 months; 95% confidence interval [CI]: 12.1-23.9 vs. 7.0 months; 95% CI: 6.1-7.9; p < 0.001) with greater PFS benefit in TP53 exon 4 or 7 mutations subgroup. Subgroup analysis showed a similar trend. The median duration of response was significantly longer in the combination group than in the EGFR-TKI group. Patients with 19 deletions or L858R mutations both achieved a significant PFS benefit with combination therapy versus EGFR-TKI alone.
CONCLUSIONS: Combination therapy had a higher efficacy than EGFR-TKI alone for patients with NSCLC having concomitant EGFR and TP53 mutations. Future prospective clinical trials are needed to determine the role of combination therapy for this patient population.