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Record W4292641407 · doi:10.1038/s41591-022-01933-w

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

2022· article· en· W4292641407 on OpenAlexaff
Solange Peters, Rafał Dziadziuszko, Alessandro Morabito, Enriqueta Felip, Shirish M. Gadgeel, Parneet Cheema, Manuel Cobo, Zoran Andrić, Carlos H. Barrios, Masafumi Yamaguchi, Éric Dansin, Pongwut Danchaivijitr, Melissa L. Johnson, Silvia Novello, Michael S. Mathisen, Sarah M. Shagan, Erica Schleifman, Jin Wang, Mark Yan, Simonetta Mocci, David Voong, David Fabrizio, David S. Shames, Todd Riehl, David R. Gandara, Tony Mok

Bibliographic record

VenueNature Medicine · 2022
Typearticle
Languageen
FieldMedicine
TopicCancer Immunotherapy and Biomarkers
Canadian institutionsWilliam Osler Health SystemUniversity of Toronto
FundersSanofi GenzymeEMD SeronoAstraZenecaGenentechAmgenTizona TherapeuticsChinese Society of Clinical OncologyAstellas PharmaY-mAbs TherapeuticsEisaiG1 TherapeuticsLunitPuma BiotechnologyRelay TherapeuticsYuhanLoxo OncologyRibon TherapeuticsSyndax PharmaceuticalsBeiGeneHong Kong Cancer FundJounce TherapeuticsRegeneron PharmaceuticalsHelsinnMirati TherapeuticsMylanDaiichi Sankyo EuropeTakeda OncologyFoundation MedicineGlaxoSmithKlineVertex PharmaceuticalsArray BioPharmaGilead SciencesTaiho PharmaceuticalMerck KGaALEO PharmaEli Lilly and CompanyCalithera BiosciencesAbbVieRevolution MedicinesExelixisSanofiNational Cancer InstituteGrifolsF. Hoffmann-La RocheRochePharmaMarOncoMed PharmaceuticalIncytePfizerBristol-Myers Squibb
KeywordsAtezolizumabMedicineOncologyInternal medicineHazard ratioLung cancerClinical endpointPopulationCohortBiomarkerRandomized controlled trialConfidence intervalCancerPembrolizumabImmunotherapy

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.002
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesInsufficient payload (model declined to judge)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Randomized trial · Consensus signal: Randomized trial
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.008
Threshold uncertainty score0.997

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0020.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0020.000
Bibliometrics0.0010.003
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0040.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.010
GPT teacher head0.313
Teacher spread0.303 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designRandomized trial
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations111
Published2022
Admission routes1
Has abstractyes

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