Department of Integrative Oncology, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, 300060, Tianjin, Tianjin, China.
Department of Esophageal Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, 300060, Tianjin, Tianjin, China.
BMC Cancer. 2023 Mar 2;23(1):198. doi: 10.1186/s12885-023-10637-4.
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.
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.
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.
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.
表皮生长因子受体（EGFR）和 TP53 突变的非小细胞肺癌（NSCLC）患者使用酪氨酸激酶抑制剂（TKI）治疗预后较差，可能优先受益于联合治疗方案。本研究旨在比较 EGFR-TKI 及其与抗血管生成药物或化疗联合治疗在真实环境中携带 EGFR 和 TP53 共突变的 NSCLC 患者中的获益。
本回顾性分析纳入了 124 例接受下一代测序治疗前存在晚期 NSCLC 伴 EGFR 和 TP53 共突变的患者。患者分为 EGFR-TKI 组和联合治疗组。本研究的主要终点为无进展生存期（PFS）。绘制 Kaplan-Meier（KM）曲线分析 PFS，并对数秩检验比较组间差异。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。
联合组包括 72 例接受 EGFR-TKI 联合抗血管生成药物或化疗治疗的患者，而 EGFR-TKI 单药组包括 52 例仅接受 TKI 治疗的患者。联合组的中位 PFS 明显长于 EGFR-TKI 组（18.0 个月；95%置信区间[CI]：12.1-23.9 比 7.0 个月；95%CI：6.1-7.9；p<0.001），TP53 外显子 4 或 7 突变亚组 PFS 获益更大。亚组分析显示出相似的趋势。联合组的中位缓解持续时间明显长于 EGFR-TKI 组。19 缺失或 L858R 突变的患者联合治疗与单独使用 EGFR-TKI 相比均获得显著的 PFS 获益。
联合治疗在 EGFR 和 TP53 共突变的 NSCLC 患者中的疗效优于 EGFR-TKI 单药治疗。需要进一步开展前瞻性临床试验以确定联合治疗在这一患者人群中的作用。
