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.

Details

Serval ID
serval:BIB_D64BF6CDC58E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
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.
Journal
Nature medicine
Author(s)
Peters S., Dziadziuszko R., Morabito A., Felip E., Gadgeel S.M., Cheema P., Cobo M., Andric Z., Barrios C.H., Yamaguchi M., Dansin E., Danchaivijitr P., Johnson M., Novello S., Mathisen M.S., Shagan S.M., Schleifman E., Wang J., Yan M., Mocci S., Voong D., Fabrizio D.A., Shames D.S., Riehl T., Gandara D.R., Mok T.
ISSN
1546-170X (Electronic)
ISSN-L
1078-8956
Publication state
Published
Issued date
09/2022
Peer-reviewed
Oui
Volume
28
Number
9
Pages
1831-1839
Language
english
Notes
Publication types: Clinical Trial, Phase III ; Journal Article ; Randomized Controlled Trial
Publication Status: ppublish
Abstract
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.
Keywords
Antibodies, Monoclonal, Humanized/adverse effects, Antineoplastic Combined Chemotherapy Protocols/adverse effects, Biomarkers, Tumor/genetics, Carcinoma, Non-Small-Cell Lung/drug therapy, Carcinoma, Non-Small-Cell Lung/genetics, Humans, Immunotherapy, Lung Neoplasms/drug therapy, Lung Neoplasms/genetics
Pubmed
Web of science
Open Access
Yes
Create date
29/08/2022 8:49
Last modification date
11/11/2022 6:39
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