EGFR T790M relative mutation purity predicts osimertinib treatment efficacy in non-small cell lung cancer patients

被引：22

作者：

Zheng, Qiufan ^{[1
]}

Hong, Shaodong ^{[1
]}

Huang, Yan ^{[1
]}

Zhao, Hongyun ^{[2
]}

Yang, Yunpeng ^{[1
]}

Hou, Xue ^{[1
]}

Zhao, Yuanyuan ^{[1
]}

Ma, Yuxiang ^{[2
]}

Zhou, Ting ^{[1
]}

Zhang, Yaxiong ^{[1
]}

Fang, Wenfeng ^{[1
]}

Zhang, Li ^{[1
]}

机构：

[1] Sun Yat Sen Univ, Ctr Canc, Collaborat Innovat Ctr Canc Med, Dept Med Oncol,State Key Lab Oncol South China, Guangzhou 510060, Guangdong, Peoples R China

[2] Sun Yat Sen Univ, Ctr Canc, Collaborat Innovat Ctr Canc Med, Dept Clin Res,State Key Lab Oncol South China, Guangzhou 510060, Guangdong, Peoples R China

来源：

CLINICAL AND TRANSLATIONAL MEDICINE | 2020年 / 9卷 / 01期

基金：

国家重点研发计划;

关键词：

T790M mutation; Allele frequency; Osimertinib; Non-small-cell lung cancer; CIRCULATING TUMOR DNA; ACQUIRED-RESISTANCE; HETEROGENEITY; NSCLC;

D O I：

10.1186/s40169-020-0269-y

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background Despite the impressive anti-tumor activity of osimertinib in epidermal growth factor receptor (EGFR) T790M-positive non-small cell lung cancer (NSCLC) patients, 30-40% of patients still show limited response. There is therefore a need to identify biomarkers that accurately predict the response to osimertinib therapy. In this study, 54 patients with targeted next-generation sequencing of circulating tumor DNA before osimertinib treatment and known T790M positivity were included. We investigated the predictive value of baseline circulating tumor DNA-derived biomarkers on osimertinib therapy. Results Baseline maximum somatic allele frequency (MSAF) level was not associated with objective response rate (ORR) (P = 0.886) and progression-free survival (PFS) (P = 0.370) of osimertinib treatment. T790M relative mutation purity (RMP, defined here as the ratio of T790M AF to MSAF) quartiles were found to be significantly associated with ORR (P for trend = 0.002) and PFS (P for trend = 0.006), and a cut off value of 0.24 identified two distinct prognostic groups [Hazard ratio (HR) = 0.36 for low T790M RMP, 95% confidence interval (CI) 0.18-0.72, P = 0.004). Additionally, although T790M relative mutation abundance (RMA, defined as T790M AF/EGFR driver AF) quartiles were not significantly associated with ORR (P for trend = 0.063), a cut off value of 0.30 also identified two distinct prognostic groups (HR = 0.43 for low T790M RMA, 95% CI 0.22-0.85, P = 0.015). However, in multivariate analysis, grouping of T790M RMP showed a better predictive value (HR = 0.46, 95% CI 0.20-1.05, P = 0.066) than T790M RMA (HR = 0.71, 95% CI 0.31-1.61, P = 0.409). Moreover, T790M RMP as continuous covariate was independently predictive of PFS (HR = 0.15, 95% CI 0.03-0.79, P =0.025), while T790M RMA was not (HR = 1.14, 95% CI 0.49-2.66, P =0.766). An external validation cohort further confirmed the T790M RMP was significantly associated with PFS of osimertinib therapy. Conclusions This study established the independent predictive role of T790M RMP in NSCLC patients receiving osimertinib treatment.

引用

页数：10

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