EGFR亚型联合TP53共突变状态对非小细胞肺癌一线奥希替尼治疗生存结局的影响
The impact of EGFR subtype combined with TP53 co-mutation status on survival outcomes with front-line osimertinib in non-small cell lung cancer (NSCLC).
作者
作者单位
- Department of Medicine, Temple University Hospital, United States.
- Biostatistics and Bioinformatics Facility, United States.
- Department of Medical Oncology, United States.
- Cancer Prevention and Control Program, Fox Chase Cancer Center, United States.
- Department of Medical Oncology, United States. Electronic address: Joseph.Treat2@fccc.edu.
摘要
中文
奥希替尼是EGFR突变非小细胞肺癌（NSCLC）的标准治疗。然而，需要更好的标志物来识别预后不良风险的患者。这是迄今评估EGFR亚型联合TP53共突变状态对一线奥希替尼治疗生存终点影响的最大规模研究。研究纳入了来自美国临床基因组数据库中接受一线奥希替尼治疗的晚期EGFR突变NSCLC患者。采用Kaplan-Meier方法估计真实世界无进展生存期（rwPFS）和总生存期（OS），并使用多变量Cox回归在调整相关临床协变量后比较结局。在606例患者中，277例（46%）为EGFR L858R突变，384例（63%）为TP53共突变，186例（30.7%）两者均有。携带L858R（对比外显子19缺失）或TP53共突变（对比野生型）均预测较差的结局（rwPFS：风险比[HR]分别为1.4，P=0.001和1.5，P<0.001；OS：HR分别为1.3，P=0.01和1.6，P<0.001）。同时携带两种标志物（L858R/TP53突变）的患者与两者均无（外显子19缺失/TP53野生型）相比，中位rwPFS（10.1 vs 21.4个月，HR 2.2，P<0.001）和OS（21.3 vs 53.4个月，HR 2.3，P<0.001）尤其短。携带EGFR L858R或TP53共突变是一线奥希替尼治疗rwPFS和OS较差的独立预测因子。同时具有两种不利改变的患者生存期最短。联合使用这些标志物进行风险分层有助于识别适合新药试验或已批准的强化治疗的患者。
English
Osimertinib is a standard therapy for EGFR-mutant NSCLC. However, markers to better identify those at risk for poor outcomes are needed. This is the largest study to date evaluating the impact of EGFR subtype combined with TP53 co-mutation status on survival endpoints with front-line osimertinib. Patients from a U.S. clinical-genomic database with advanced EGFR-mutant NSCLC receiving front-line osimertinib were studied. Real-world progression-free survival (rwPFS) and overall survival (OS) were determined using Kaplan-Meier methods, and multivariable Cox regression compared outcomes after accounting for relevant clinical covariates. Of 606 patients, 277 (46%) had EGFR L858R, 384 (63%) had TP53 co-mutations, and 186 (30.7%) had both. Bearing L858R vs. exon 19 deletions (rwPFS: hazard ratio [HR] 1.4, P = 0.001; OS: HR 1.3, P = 0.01) or a TP53 co-mutation vs. wildtype (rwPFS: HR 1.5, P < 0.001; OS: HR 1.6, P < 0.001) predicted inferior outcomes. Especially short median rwPFS (10.1 vs. 21.4 months, HR 2.2, P < 0.001) and OS (21.3 vs. 53.4 months, HR 2.3, P < 0.001) were observed in patients with both markers (L858R/TP53-mutant) as compared to neither (exon 19 deletion/TP53-wildtype). Having EGFR L858R or a TP53 co-mutation were independent predictors of inferior rwPFS and OS with front-line osimertinib. Patients with both unfavorable alterations had the shortest survival. Risk stratifying using a combination of these markers can assist in identifying patients for novel trials or approved intensified therapies.
分类与指标
- 研究类型
- 临床研究
- 病种
- 肺癌
- JCR 分区
- Q1
- 影响因子
- 5.3
- 新锐分区
- 2区