真实世界人群中表皮生长因子受体敏感突变的非小细胞肺癌患者采用表皮生长因子受体酪氨酸激酶抑制剂联合贝伐珠单抗作为一线治疗的疗效和获得性耐药的研究。
Investigation of efficacy and acquired resistance for EGFR-TKI plus bevacizumab as first-line treatment in patients with EGFR sensitive mutant non-small cell lung cancer in a Real world population.
机构信息
Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, China.
Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, China; Graduate School, University of South China, Hengyang, Hunan, 421001, China.
出版信息
Lung Cancer. 2020 Mar;141:82-88. doi: 10.1016/j.lungcan.2020.01.009. Epub 2020 Jan 13.
OBJECTIVES
We aimed to investigate the clinical efficacy of EGFR tyrosine kinase inhibitor (TKI, T) plus bevacizumab (an antiangiogenic therapy, A) in a real-world population and to provide insights into their mechanism of resistance.
METHODS
This study included 256 NSCLC patients harboring EGFR sensitizing mutations (EGFR 19del and L858R) who underwent nextgeneration sequencing (NGS) with 168-gene panel prior to treatment between Jan 2015 to Aug 2018. Cohort A included 60 patients treated with A + T; while cohort B consisted of 120 patients treated with EGFR-TKI monotherapy with the patients identified using Propensity Score Matching (Ratio of 1:2). Clinical outcomes and potential resistance mechanism were evaluated.
RESULTS
Baseline clinical characteristics were not significantly different between Cohort A and B. Compared with cohort B, cohort A had significantly better overall response rate (95% vs 74.2%, p = 0.001) and longer median progression-free survival (PFS, 16.5m vs.12.0 m, HR = 0.7, p = 0.001). Until Jan 2019, 31 and 103 patients in cohort A and B, respectively, were evaluated with progressive disease and underwent tissue re-biopsy and NGS profiling with 168-gene panel. In cohort B, T790M was the predominant acquired resistance mechanism, detected in 51.5% (53/103) of progressive tumors, followed by amplifications in EGFR (15.5%, 16/103) and MET (6.8%, 7/103). Contrastingly, cohort A had a significantly lower rate of T790 M mutation (35.5%, 11/31, p = 0.0003), followed by mutations in TP53 (29.0%, 9/31), RB1 (9.7%, 3/31), SMAD4 (3.2%, 1/31) and EGFR V834 L (3.2%, 1/31) and amplifications in EGFR (9.7%, 3/31), and MET(6.5%, 2/31).
CONCLUSION
Treatment with first-line A + T significantly extends the time to progression and increases the response rate with acceptable safety profile. T790 M was the most common acquired resistance mechanism but it was less common in patients who received A + T.
目的
我们旨在研究表皮生长因子受体酪氨酸激酶抑制剂（TKI，T）联合贝伐单抗（一种抗血管生成治疗，A）在真实世界人群中的临床疗效，并探讨其耐药机制。
方法
本研究纳入了 256 例接受下一代测序（NGS）检测携带表皮生长因子受体敏感突变（EGFR 19 缺失和 L858R）的非小细胞肺癌（NSCLC）患者，NGS 检测采用 168 基因panel。A 队列包括 60 例接受 A + T 治疗的患者；B 队列包括 120 例接受 EGFR-TKI 单药治疗的患者，采用倾向评分匹配（1:2）法确定患者。评估临床结局和潜在的耐药机制。
结果
A 队列和 B 队列的基线临床特征无显著差异。与 B 队列相比，A 队列的总缓解率（95% vs 74.2%，p = 0.001）和中位无进展生存期（PFS，16.5m vs.12.0 m，HR = 0.7，p = 0.001）均显著改善。截至 2019 年 1 月，A 队列和 B 队列分别有 31 例和 103 例患者因病情进展进行了组织再活检和 168 基因panel 的 NGS 分析。在 B 队列中，T790M 是主要的获得性耐药机制，在 51.5%（53/103）的进展性肿瘤中检测到，其次是 EGFR 扩增（15.5%，16/103）和 MET 扩增（6.8%，7/103）。相比之下，A 队列的 T790M 突变率显著较低（35.5%，11/31，p = 0.0003），其次是 TP53 突变（29.0%，9/31）、RB1 扩增（9.7%，3/31）、SMAD4 突变（3.2%，1/31）和 EGFR V834L 突变（3.2%，1/31），以及 EGFR 扩增（9.7%，3/31）和 MET 扩增（6.5%，2/31）。
结论
一线 A + T 治疗可显著延长进展时间，提高缓解率，且具有可接受的安全性。T790M 是最常见的获得性耐药机制，但在接受 A + T 治疗的患者中较少见。
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