Evaluation of plasma EGFR mutation as an early predictor of response of erlotinib plus bevacizumab treatment in the NEJ026 study
Evaluation of plasma EGFR mutation as an early predictor of response of erlotinib plus bevacizumab treatment in the NEJ026 study
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DOI：
10.1016/j.ebiom.2020.102861
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发表时间：
2020-07-01
期刊：
影响因子：
11.1
通讯作者：
Maemondo, Makoto
中科院分区：
文献类型：
--
作者：
Fukuhara, Tatsuro;Saito, Haruhiro;Maemondo, Makoto
背景资料：NEJ 026 III期研究表明，厄洛替尼和贝伐珠单抗（BE）治疗的EGFR突变NSCLC患者的无进展生存期（PFS）显著优于厄洛替尼单药治疗的患者（E）。本研究包括血浆循环肿瘤DNA（ctDNA）中EGFR突变状态与TKI单药治疗或联合治疗疗效之间关系的前瞻性分析。方法：在治疗开始时（P0）、治疗开始后6周（P1）和确认疾病进展时（P2），从NEJ 026中招募的患者中收集血浆样品。采用改良的PNA-LNA PCR钳方法分析血浆ctDNA。结果：68%的病例在P0时检测到血浆激活EGFR突变（aEGFR）;无血浆aEGFR的患者PFS较长。两组P2时T790 M突变频率相似：BE组8例（19.0%），E组11例（20.8%）。根据aEGFR特征，在三组中评价PFS：A型[P0（-），P1（-）]、B型[P0（+），P1（-）]和C型[P0（+），P1（+）]。这表明BE比E更有效，并且BE与所有类型的PFS改善相关。解释：治疗前血浆aEGFR状态有可能成为TKI疗效反应的早期预测因子。监测血浆aEGFR突变将有助于选择和继续BE或E治疗。
Background: The NEJ026 Phase 3 study demonstrated that erlotinib and bevacizumab (BE)-treated NSCLC patients with EGFR mutations had significantly better progression-free survival (PFS) than those treated with erlotinib alone (E). This study included a prospective analysis of the relationship between the mutational status of EGFR in plasma circulating tumor DNA (ctDNA) and the efficacy of TKI monotherapy or combination therapy. We describe these results herein.Methods: Plasma samples were collected from patients enrolled in NEJ026 at the start of treatment (P0), 6 weeks after the start of treatment (P1), and upon confirmation of progressive disease (P2). Plasma ctDNA was analyzed using a modified PNA-LNA PCR clamp method. PFS and OS according to EGFR status at the time of plasma collection were evaluated.Findings: Plasma activating EGFR mutation (aEGFR) at P0 was detected in 68% of cases; patients without plasma aEGFR had longer PFS. The frequency of T790M mutation at P2 was similar in both arms: 8 (19.0%) in BE and 11 (20.8%) in E. Based on the aEGFR profiles, PFS was evaluated among three groups: type A [P0(-), P1 (-)], type B [P0(+), P1(-)], and type C [P0(+), P1(+)]. This revealed that BE was more efficacious than E, and that BE was associated with improved PFS in all types.Interpretation: Pre-treatment plasma aEGFR status have a potential of early predictor of response of TKI efficacy. Monitoring plasma aEGFR mutation will contribute to selection and continuation of treatment with BE or E.