State Key Laboratory of Oncology in Southern China, Department of Thoracic Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Med Oncol. 2014 Jan;31(1):810. doi: 10.1007/s12032-013-0810-6. Epub 2013 Dec 14.
There is no consensus in the salvage treatment for non-small-cell lung cancer (NSCLC) with acquired resistance to primary epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). Fifty-one consecutive EGFR-mutated NSCLC patients with TKI retreatment after acquired resistance were enrolled in this study. The quantitation of mutation abundance was performed by real-time fluorescent quantitative PCR. The correlation between mutation abundance and outcomes of readministrated TKI was analyzed by survival analysis. Patients with high (H) mutation abundance (24/51) had a significantly (log-rank, P < 0.05) longer (5.27-2.53 months) median progression-free survival (PFS), compared with the low (L) abundance group (27/51), whereas the median overall survival showed no difference (21.00-18.20 months, log-rank P = .403) between the two groups. Objective response and disease control rates in group H and group L regarding the second round TKI treatment were 8.3, 70.8 and 0, 48.1 %, respectively. Groupings with different mutation abundances were significantly associated with PFS under multivariate Cox proportional hazards regression model [hazard ratio (HR) for group H vs. L, 0.527; P = .036]. Mutation abundance affects the efficacy of EGFR-TKIs readministration in NSCLC with acquired resistance. The quantitative mutation abundance of EGFR may be a potential predictor for selecting optimal patients to readministrate EGFR-TKIs after acquired resistance to primary TKI.
对于原发性表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)获得性耐药的非小细胞肺癌(NSCLC),挽救治疗尚无共识。本研究纳入了 51 例连续的 EGFR 突变 NSCLC 患者,这些患者在获得性耐药后接受了 TKI 再治疗。通过实时荧光定量 PCR 进行突变丰度定量。通过生存分析分析了重新给予 TKI 的突变丰度与结局的相关性。高(H)突变丰度(24/51)患者的无进展生存期(PFS)明显更长(5.27-2.53 个月)(log-rank,P < 0.05),与低(L)丰度组(27/51)相比,而两组的中位总生存期无差异(21.00-18.20 个月,log-rank P =.403)。第二轮 TKI 治疗中,H 组和 L 组的客观缓解率和疾病控制率分别为 8.3%、70.8%和 0%、48.1%。多变量 Cox 比例风险回归模型显示,不同突变丰度组与 PFS 显著相关[H 组与 L 组的危险比(HR)为 0.527;P =.036]。突变丰度影响 EGFR-TKI 再治疗在 NSCLC 获得性耐药中的疗效。EGFR 的定量突变丰度可能是选择最佳患者重新给予 EGFR-TKI 的潜在预测因子,这些患者对原发性 TKI 耐药。