Department of Medical Oncology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266005, Shandong Province, China.
BMC Cancer. 2020 Apr 16;20(1):328. doi: 10.1186/s12885-020-06805-5.
The prognostic significance of TP53 concurrent mutations in patients with epidermal growth factor receptor (EGFR)- or anaplastic lymphoma kinase (ALK)- mutated advanced non-small-cell lung cancer (NSCLC) who received EGFR-tyrosine kinase inhibitors (TKIs) or ALK-TKIs based targeted therapy remains controversial. Therefore, the present meta-analysis was performed to investigate the association between TP53 concurrent mutations and prognosis of patients with advanced NSCLC undergoing EGFR-TKIs or ALK-TKIs treatments.
Eligible studies were identified by searching the online databases PubMed, Embase, Medline, The Cochrane library and Web of Science. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to clarify the correlation between TP53 mutation status and prognosis of patients. This meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.
In total, 15 studies with 1342 patients were included for final analysis. Overall, concurrent TP53 mutation was associated with unfavorable progression-free survival (PFS) (HR = 1.88, 95%CI: 1.59-2.23, p < 0.001, I = 0.0%, P = 0.792) and overall survival (OS) (HR = 1.92, 95%CI: 1.55-2.38, p < 0.001, I = 0.0%, P = 0.515). Subgroup analysis based on type of targeted therapy (EGFR-TKIs or ALK-TKIs, pathological type of cancer (adenocarcinoma only or all NSCLC subtypes) and line of treatment (first-line only or all lines) all showed that TP53 mutations was associated with shorter survivals of patients with EGFR-TKIs or ALK-TKIs treatments. Particularly, in patients with first-line EGFR-TKIs treatment, significantly poorer prognosis was observed in patients with TP53 concurrent mutations (pooled HR for PFS: 1.69, 95% CI 1.25-2.27, P < 0.001, I = 0.0%, P = 0.473; pooled HR for OS: 1.94, 95% CI 1.36-2.76, P < 0.001, I = 0.0%, P = 0.484). Begg's funnel plots and Egger's tests indicated no significant publication bias in this study.
This meta-analysis indicated that concurrent TP53 mutations was a negative prognostic factor and associated with poorer outcomes of patients with EGFR-TKIs or ALK-TKIs treatments in advanced NSCLC. In addition, our study provided evidence that TP53 mutations might be involved in primary resistance to EGFR-TKIs treatments in patients with sensitive EGFR mutations in advanced NSCLC.
表皮生长因子受体（EGFR）或间变性淋巴瘤激酶（ALK）突变的晚期非小细胞肺癌（NSCLC）患者接受 EGFR 酪氨酸激酶抑制剂（TKI）或 ALK-TKI 靶向治疗后，TP53 并发突变的预后意义仍存在争议。因此，本研究进行了荟萃分析，以探讨 TP53 并发突变与接受 EGFR-TKI 或 ALK-TKI 治疗的晚期 NSCLC 患者预后之间的关系。
通过检索在线数据库 PubMed、Embase、Medline、The Cochrane library 和 Web of Science，确定了符合条件的研究。使用 95%置信区间（CI）计算风险比（HR），以阐明 TP53 突变状态与患者预后之间的相关性。该荟萃分析是根据系统评价和荟萃分析的首选报告项目（PRISMA）声明进行的。
共纳入 15 项研究，包含 1342 名患者进行最终分析。总体而言，TP53 并发突变与无进展生存期（PFS）（HR=1.88，95%CI：1.59-2.23，p<0.001，I=0.0%，P=0.792）和总生存期（OS）（HR=1.92，95%CI：1.55-2.38，p<0.001，I=0.0%，P=0.515）较差相关。基于靶向治疗类型（EGFR-TKI 或 ALK-TKI、癌症病理类型（腺癌或所有 NSCLC 亚型）和治疗线数（一线或所有线数）的亚组分析均表明，TP53 突变与 EGFR-TKI 或 ALK-TKI 治疗患者的生存时间较短有关。特别是在接受一线 EGFR-TKI 治疗的患者中，TP53 并发突变的患者预后明显较差（PFS 的合并 HR：1.69，95%CI 1.25-2.27，p<0.001，I=0.0%，P=0.473；OS 的合并 HR：1.94，95%CI 1.36-2.76，p<0.001，I=0.0%，P=0.484）。Begg 漏斗图和 Egger 检验表明本研究无显著发表偏倚。
这项荟萃分析表明，TP53 并发突变是一个负预后因素，与 EGFR-TKI 或 ALK-TKI 治疗晚期 NSCLC 患者的结局较差相关。此外，我们的研究提供了证据表明，TP53 突变可能参与了晚期 NSCLC 中敏感 EGFR 突变患者对 EGFR-TKI 治疗的原发性耐药。
