阿替利珠单抗对比化疗在具有高血基肿瘤突变负荷的晚期或转移性NSCLC: BFAST队列C随机3期试验的初步分析

SCI

15 September 2022

Atezolizumab versus chemotherapy in advanced or metastatic NSCLC with high blood-based tumor mutational burden: primary analysis of BFAST cohort C randomized phase 3 trial 

(Nature Medicine, IF: 87.241)

Peters S, Dziadziuszko R, Morabito A, et al. Atezolizumab versus chemotherapy in advanced or metastatic NSCLC with high blood-based tumor mutational burden: primary analysis of BFAST cohort C randomized phase 3 trial. 

ABSTRACT摘要

Tumor mutational burden (TMB) is being explored as a predictive biomarker for cancer immunotherapy outcomes in non-small cell lung cancer. BFAST (NCT03178552)—an open-label, global, multicohort trial—evaluated the safety and efficacy of first-line targeted therapies or immunotherapy in patients with unresectable Stage IIIB or IV advanced or metastatic non-small cell lung cancer who were selected for biomarker status using blood-based targeted next-generation sequencing. In the Phase 3 cohort C evaluating blood-based (b)TMB as a biomarker of atezolizumab efficacy, patients with bTMB of ≥10 (N = 471) were randomized 1:1 to receive atezolizumab or platinum-based chemotherapy per local standard of care. Cohort C did not meet its primary endpoint of investigator-assessed progression-free survival in the population with bTMB of ≥16 (hazard ratio, 0.77; 95% confidence interval: 0.59, 1.00; P = 0.053). Adverse events leading to treatment withdrawal occurred in 10% of patients in the atezolizumab arm and 20% in the chemotherapy arm. Adverse events of special interest occurred in 42% of patients in the atezolizumab arm and 26% in the chemotherapy arm. A prespecified exploratory analysis compared the bTMB clinical trial assay with the FoundationOne Liquid Companion Diagnostic assay and showed high concordance between assays. Additional exploration of bTMB to identify optimal cutoffs, confounding factors, assay improvements or cooperative biomarkers is warranted.

肿瘤突变负荷（TMB）正被探索作为非小细胞肺癌免疫治疗结果的预测生物标志物。BFAST (NCT03178552)是一项非盲、全球性、多队列试验，使用基于血液的靶向二代测序技术，评估了不可切除的IIIB或IV期晚期或转移性非小细胞肺癌患者的一线靶向治疗或免疫治疗的安全性和有效性。在3期队列C研究中，血基TMB（bTMB）作为评估阿替利珠单抗有效性的生物标志物，bTMB≥10 (N = 471)的患者按1:1随机分组，按照当地治疗标准接受阿替利珠单抗或铂基化疗。队列C在bTMB≥16的人群中不满足研究人员评估的无进展生存期的主要终点(HR，0.77；95%CI：0.59，1.00;P = 0.053)。在阿替利珠单抗组和化疗组中分别有10%和20%的患者发生导致治疗终止的不良事件。在阿替利珠单抗组和化疗组中分别有42%和26%的患者发生了特殊的不良事件。一项预先指定的探索性分析将bTMB临床试验分析与FoundationOne Liquid Companion Diagnostic分析进行了比较，结果显示各分析之间具有高度的一致性。有必要对bTMB进行额外的探索，以确定最佳的截止点、混杂因素、分析改进或合作生物标志物。

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