Abstract：
Purpose: The purpose of this study was to investigate the effect of MYC and TP53 comutations on the clinical efficacy of EGFR tyrosine kinase inhibitors (TKIs) in Chinese patients with advanced EGFR-positive nonsmall-cell lung cancer (NSCLC). Patients and methods: Tissue samples and information from 65 patients with advanced NSCLC in Northern Jiangsu People\'s Hospital were collected and analyzed by next-generation sequencing (NGS). Progression-free survival (PFS) and total survival (OS) were the main endpoints, and the objective response rate (ORR) and disease control rate (DCR) were the secondary endpoints. Result: Among 65 patients, 17 had TP53 and MYC wild-type mutations (WT/WT), 36 had TP53 mutant and MYC wild-type mutations (TP53/WT), and 12 had coexisting MYC/TP53 mutations (MYC/TP53). When 12 patients with MYC/TP53 comutation were compared with the other two groups (TP53/WT, WT/WT), mPFS and mOS are significantly lower than those in the other two groups (mPFS: 4.1 months vs 6.0 months, 12.3 months, HR: 0.769, 95% CI: 4.592-7.608, P = .047. mOS: 14.6 months vs 24.1 months, 31.5 months, HR: 3.170, 95% CI: 18.786-31.214, P < .001), and the ORR, DCR of patients with MYC/TP53 comutation was lower than that of the other two groups (ORR, 25% vs 44.4%, 70.6%, P = .045. DCR, 58.3% vs 72.2%, 82.4%, P = .365). Conclusion: Patients with MYC/TP53 comutations with EGFR-positive advanced NSCLC are more likely to develop drug resistance after early treatment with EGFR-TKIs and have a worse clinical outcome.
摘要：
目的：本研究的目的是探讨MYC和TP53融合对EGFR酪氨酸激酶抑制剂（TKIs）在中国晚期EGFR阳性非小细胞肺癌（NSCLC）患者中的临床疗效的影响。患者和方法：收集苏北人民医院65例晚期非小细胞肺癌患者的组织样本和信息，并进行下一代测序（NGS）分析。无进展生存期（PFS）和总生存期（OS）是主要终点，客观缓解率（ORR）和疾病控制率（DCR）是次要终点。结果：在65例患者中，17个有TP53和MYC野生型突变（WT/WT），36具有TP53突变体和MYC野生型突变（TP53/WT），12例同时存在MYC/TP53突变（MYC/TP53）。当12例MYC/TP53合并患者与其他两组(TP53/WT,WT/WT)，mPFS和mOS显著低于其他两组(mPFS:4.1个月vs6.0个月,12.3个月,HR：0.769，95%CI：4.592-7.608，P=0.047。MOS：14.6个月vs24.1个月，31.5个月，HR：3.170，95%CI：18.786-31.214，P<.001），和ORR，MYC/TP53合并患者的DCR低于其他两组（ORR，25%vs44.4%，70.6%,P=.045。DCR,58.3%vs72.2%，82.4%,P=.365）。结论：MYC/TP53合并EGFR阳性的晚期NSCLC患者在早期接受EGFR-TKIs治疗后更容易出现耐药，临床预后较差。
