a Department of Internal Medicine , The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital , Zhengzhou , China.
b Department of Molecular Pathology , The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital , Zhengzhou , China.
Cancer Biol Ther. 2018 Aug 3;19(8):687-694. doi: 10.1080/15384047.2018.1450115. Epub 2018 Apr 13.
To investigate the influence of mutation abundance and sites of epidermal growth factor receptor (EGFR) on therapeutic efficacies of EGFR-tyrosine kinase inhibitor (EGFR-TKIs) treatments of patients with advanced non-small cell lung carcinoma (NSCLC).
EGFR mutational sites and mutation abundance were analyzed by amplification refractory mutation system (ARMS) in paraffin-embedded tissue sections taken from primary or metastatic tumors of 194 NSCLC patients.
The median progression-free survival (PFS) time of the enrolled patients was 9.3 months (95% CI, 8.2-10.8 months). The PFS was significantly different with EGFR gene mutation abundance after EGFR-TKI therapy (P = 0.014). The median PFS was significantly longer when the cut-off value of EGFR mutation abundance of exon 19 or exon 21, and solely exon 19 was > 26.7% and 61.8%, respectively. For patients who received EGFR-TKI as first-line treatment, the median PFS was significantly longer in the high mutation abundance group than in the low mutation abundance group (12.7 vs 8.7 months, P = 0.002).
The PFS benefits were greater in patients with a higher abundance of exon 19 deletion mutations in the EGFR gene after EGFR-TKI treatment and first line EGFR-TKI treatment led to improved PFS in high mutation abundance patients.
探讨表皮生长因子受体(EGFR)突变丰度和突变位点对晚期非小细胞肺癌(NSCLC)患者接受 EGFR 酪氨酸激酶抑制剂(EGFR-TKIs)治疗疗效的影响。
采用扩增阻滞突变系统(ARMS)检测 194 例 NSCLC 患者的原发或转移肿瘤石蜡包埋组织切片中 EGFR 突变位点和突变丰度。
入组患者的中位无进展生存期(PFS)为 9.3 个月(95%CI:8.2-10.8 个月)。EGFR-TKI 治疗后 EGFR 基因突变丰度与 PFS 显著相关(P=0.014)。EGFR 外显子 19 或外显子 21 突变丰度截断值>26.7%和 61.8%时,中位 PFS 明显延长;仅外显子 19 突变丰度截断值>26.7%时,中位 PFS 明显延长。对于接受 EGFR-TKI 作为一线治疗的患者,高突变丰度组的中位 PFS 明显长于低突变丰度组(12.7 个月比 8.7 个月,P=0.002)。
EGFR-TKI 治疗后 EGFR 基因外显子 19 缺失突变丰度较高的患者 PFS 获益更大,一线 EGFR-TKI 治疗可改善高突变丰度患者的 PFS。