EGFR T790M突变丰度对奥希替尼治疗晚期非小细胞肺癌疗效的影响

Relationship Between Abundance of EGFR T790M Mutation and Efficacy of Osimertinib in Treatment of Advanced Non-small Cell Lung Cancer Patients

[目的]分析奥希替尼治疗晚期非小细胞肺癌疗效,并探索ddPCR方法外周血检测表皮生长因子(epidermal growth factor,EGFR)T790M突变的丰度与奥希替尼疗效之间的关系。[方法]回顾性分析104例接受奥希替尼治疗的Ⅲb~Ⅳ期非小细胞癌肺癌患者,采用ddPCR法测定外周血T790M突变丰度,采用Kaplan-Meier法和Cox模型进行生存预后分析,并探索疗效相关T790M突变丰度的界值。[结果]外周血EGFR T790M突变丰度中位值为0.89%(0.02%~35.10%)。将突变丰度分为<5.00%和≥5.00%两组,客观缓解率分别为46.5%和88.9%(P=0.001),中位无进展生存期分别为8.80个月和21.83个月(P=0.039)。Cox回归分析显示,初治时基因类型(EGFR 19外显子缺失和21外显子L858R突变)、PS评分、外周血EGFR T790M突变丰度分组(<5.00%和≥5.00%)是奥希替尼治疗患者PFS的独立影响因素。[结论]EGFR T790M突变丰度可能可预测奥希替尼治疗的晚期EGFR T790M突变NSCLC患者的有效率和无进展生存期。

[Objective]To investigate the relationship between abundance of EGFR T790 M mutation and the efficacy of osimertinib in treatment of patients with advanced non-small cell lung cancer(NSCLC).[Methods]One hundred and four stageⅢb~ⅣNSCLC patients treated with osimertinib were included in the study.The abundance of peripheral blood T790 M mutation as determined with dd PCR method,the survival of patients was analyzed with Kaplan-Meier method,the related factors for patients’survival were analyze with Cox model,the cutoff value of T790 M mutation abundance for predicting therapeutic efficacy was explored.[Results]The median mutation abundance of peripheral blood EGFR T790 M was 0.89%(0.02%~35.10%).For patients with mutation abundance<5.00% and≥5.00%,the objective response rate(ORR)was 46.5% and 88.9%(P=0.001),and the median progression-free survival(PFS)was 8.80 months and 21.83 months(P=0.039),respectively.Cox regression analysis showed that genotype(EGFR 19 exon deletion and 21 exon L858 R mutation),PS score,and peripheral blood EGFR T790 M mutation abundance(<5.00% and≥5.00%)were independent influencing factors for PFS in patients with osimertinib treatment.[Conclusion]The abundance of EGFR T790 M mutation determined by dd PCR may predict the response and progression-free survival in patients with advanced NSCLC treated with osimertinib.