PDF(Pubmed)
Abstract：
UNASSIGNED: An exploratory, proof-of-concept, liquid biopsy addendum to examine biomarkers within cell-free DNA (cfDNA) in the RELAY phase 3, randomized, double-blind, placebo-controlled study was conducted. RELAY showed improved progression-free survival (PFS) with ramucirumab (RAM), a human immunoglobulin G1 vascular endothelial growth factor receptor 2 antagonist, plus erlotinib (ERL), a tyrosine kinase inhibitor, compared with placebo (PL) plus ERL.
UNASSIGNED: Treatment-naïve patients with endothelial growth factor receptor (EGFR)-mutated metastatic non-small cell lung cancer were randomized (1:1) to RAM + ERL or PL + ERL. Plasma samples were collected at baseline, on treatment, and at 30-day post-study treatment discontinuation follow-up. Baseline and treatment-emergent gene alterations and EGFR-activating mutation allele counts were investigated by next-generation sequencing (NGS) and droplet digital polymerase chain reaction (ddPCR), respectively. cfDNA concentration and fragment size were evaluated by real-time polymerase chain reaction and the BioAnalyzer. Patients with a valid baseline plasma sample were included (70 RAM + ERL, 61 PL + ERL).
UNASSIGNED: TP53 mutation was the most frequently co-occurring baseline gene alteration (43%). Post-study treatment discontinuation EGFR T790M mutation rates were 54.5% (6/11) and 41.2% (7/17) by ddPCR, and 22.2% (2/9) and 29.4% (5/17) by NGS, in the RAM + ERL and PL + ERL arms, respectively. EGFR-activating mutation allele count decreased at Cycle 4 in both treatment arms and was sustained at follow-up with RAM + ERL. PFS improved for patients with no detectable EGFR-activating mutation at Cycle 4 vs. those with detectable EGFR-activating mutation. Total cfDNA concentration increased from baseline at Cycle 4 and through to follow-up with RAM + ERL. cfDNA fragment size was similar between treatment arms at baseline [mean (standard deviation) base pairs: RAM + ERL, 173.4 (2.6); PL + ERL, 172.9 (3.2)] and was shorter at Cycle 4 with RAM + ERL vs. PL + ERL [169.5 (2.8) vs. 174.1 (3.3), respectively; P<0.0001]. Baseline vs. Cycle 4 paired analysis showed a decrease in cfDNA fragment size for 84% (48/57) and 23% (11/47) of patient samples in the RAM + ERL and PL + ERL arms, respectively.
UNASSIGNED: EGFR-activating mutation allele count was suppressed, total cfDNA concentration increased, and short fragment-sized cfDNA increased with RAM + ERL, suggesting the additional anti-tumor effect of RAM may contribute to the PFS benefit observed in RELAY with RAM + ERL vs. PL + ERL.
UNASSIGNED: ClinicalTrials.gov; identifier: NCT02411448.
UNASSIGNED: Treatment-naïve patients with endothelial growth factor receptor (EGFR)-mutated metastatic non-small cell lung cancer were randomized (1:1) to RAM + ERL or PL + ERL. Plasma samples were collected at baseline, on treatment, and at 30-day post-study treatment discontinuation follow-up. Baseline and treatment-emergent gene alterations and EGFR-activating mutation allele counts were investigated by next-generation sequencing (NGS) and droplet digital polymerase chain reaction (ddPCR), respectively. cfDNA concentration and fragment size were evaluated by real-time polymerase chain reaction and the BioAnalyzer. Patients with a valid baseline plasma sample were included (70 RAM + ERL, 61 PL + ERL).
UNASSIGNED: TP53 mutation was the most frequently co-occurring baseline gene alteration (43%). Post-study treatment discontinuation EGFR T790M mutation rates were 54.5% (6/11) and 41.2% (7/17) by ddPCR, and 22.2% (2/9) and 29.4% (5/17) by NGS, in the RAM + ERL and PL + ERL arms, respectively. EGFR-activating mutation allele count decreased at Cycle 4 in both treatment arms and was sustained at follow-up with RAM + ERL. PFS improved for patients with no detectable EGFR-activating mutation at Cycle 4 vs. those with detectable EGFR-activating mutation. Total cfDNA concentration increased from baseline at Cycle 4 and through to follow-up with RAM + ERL. cfDNA fragment size was similar between treatment arms at baseline [mean (standard deviation) base pairs: RAM + ERL, 173.4 (2.6); PL + ERL, 172.9 (3.2)] and was shorter at Cycle 4 with RAM + ERL vs. PL + ERL [169.5 (2.8) vs. 174.1 (3.3), respectively; P<0.0001]. Baseline vs. Cycle 4 paired analysis showed a decrease in cfDNA fragment size for 84% (48/57) and 23% (11/47) of patient samples in the RAM + ERL and PL + ERL arms, respectively.
UNASSIGNED: EGFR-activating mutation allele count was suppressed, total cfDNA concentration increased, and short fragment-sized cfDNA increased with RAM + ERL, suggesting the additional anti-tumor effect of RAM may contribute to the PFS benefit observed in RELAY with RAM + ERL vs. PL + ERL.
UNASSIGNED: ClinicalTrials.gov; identifier: NCT02411448.
摘要：
■探索性的，概念验证,液体活检附录，以检查RELAY3期无细胞DNA（cfDNA）中的生物标志物，双盲,进行了安慰剂对照研究.RELAY显示雷莫西单抗（RAM）改善了无进展生存期（PFS），人免疫球蛋白G1血管内皮生长因子受体2拮抗剂，加厄洛替尼（ERL），酪氨酸激酶抑制剂，与安慰剂（PL）加ERL相比。
■将未治疗的内皮生长因子受体（EGFR）突变的转移性非小细胞肺癌患者随机（1：1）接受RAM+ERL或PL+ERL治疗。在基线时收集血浆样品，关于治疗，并在研究后30天停止治疗随访。通过下一代测序（NGS）和液滴数字聚合酶链反应（ddPCR）研究了基线和治疗引起的基因改变和EGFR激活突变等位基因计数。分别。通过实时聚合酶链反应和BioAnalyzer评估cfDNA浓度和片段大小。纳入具有有效基线血浆样本的患者(70RAM+ERL，61PL+ERL)。
■TP53突变是最常同时发生的基线基因改变（43％）。研究后停止治疗的EGFRT790M突变率分别为54.5%(6/11)和41.2%(7/17)。NGS分别为22.2%(2/9)和29.4%(5/17)，在RAM+ERL和PL+ERL臂中，分别。EGFR激活突变等位基因计数在第4周期在两个治疗组中降低,并且在用RAM+ERL的随访中持续。在第4周期没有检测到的EGFR激活突变的患者的PFS改善与那些具有可检测的EGFR激活突变的人。总cfDNA浓度在第4周期从基线增加,直到用RAM+ERL随访。cfDNA片段大小在基线[平均值（标准偏差）碱基对：RAM+ERL，173.4（2.6）；PL+ERL，172.9（3.2）]，在第4周期，RAM+ERL与PL+ERL[169.5（2.8）vs.174.1(3.3),分别为；P<0.0001]。基线与第4周期配对分析显示，在RAM+ERL和PL+ERL组中，84%（48/57）和23%（11/47）的患者样本的cfDNA片段大小减少，分别。
■EGFR激活突变等位基因计数被抑制，总cfDNA浓度增加，短片段大小的cfDNA随着RAM+ERL而增加，提示RAM的额外抗肿瘤作用可能有助于在RAM+ERL的RELAY中观察到的PFS益处。PL+ERL。
■ClinicalTrials.gov；标识符：NCT02411448。
■将未治疗的内皮生长因子受体（EGFR）突变的转移性非小细胞肺癌患者随机（1：1）接受RAM+ERL或PL+ERL治疗。在基线时收集血浆样品，关于治疗，并在研究后30天停止治疗随访。通过下一代测序（NGS）和液滴数字聚合酶链反应（ddPCR）研究了基线和治疗引起的基因改变和EGFR激活突变等位基因计数。分别。通过实时聚合酶链反应和BioAnalyzer评估cfDNA浓度和片段大小。纳入具有有效基线血浆样本的患者(70RAM+ERL，61PL+ERL)。
■TP53突变是最常同时发生的基线基因改变（43％）。研究后停止治疗的EGFRT790M突变率分别为54.5%(6/11)和41.2%(7/17)。NGS分别为22.2%(2/9)和29.4%(5/17)，在RAM+ERL和PL+ERL臂中，分别。EGFR激活突变等位基因计数在第4周期在两个治疗组中降低,并且在用RAM+ERL的随访中持续。在第4周期没有检测到的EGFR激活突变的患者的PFS改善与那些具有可检测的EGFR激活突变的人。总cfDNA浓度在第4周期从基线增加,直到用RAM+ERL随访。cfDNA片段大小在基线[平均值（标准偏差）碱基对：RAM+ERL，173.4（2.6）；PL+ERL，172.9（3.2）]，在第4周期，RAM+ERL与PL+ERL[169.5（2.8）vs.174.1(3.3),分别为；P<0.0001]。基线与第4周期配对分析显示，在RAM+ERL和PL+ERL组中，84%（48/57）和23%（11/47）的患者样本的cfDNA片段大小减少，分别。
■EGFR激活突变等位基因计数被抑制，总cfDNA浓度增加，短片段大小的cfDNA随着RAM+ERL而增加，提示RAM的额外抗肿瘤作用可能有助于在RAM+ERL的RELAY中观察到的PFS益处。PL+ERL。
■ClinicalTrials.gov；标识符：NCT02411448。
