Evidence map›Paper›PMID 35422531›Full record

Trial reportNature medicine2022

Blood-based tumor mutational burden as a biomarker for atezolizumab in non-small cell lung cancer: the phase 2 B-F1RST trial.

Edward S Kim, Vamsidhar Velcheti, Tarek Mekhail, Cindy Yun, Sarah M Shagan, Sylvia Hu, Young Kwang Chae, Ticiana A Leal, Jonathan E Dowell, Michaela L Tsai and 8 more

Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Nature medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02848651 (A Phase II Single-Arm Study of Atezolizumab Monotherapy in Locally Advanced or Metastatic Non-Small Cell Lung Cancer), which is not on this map. Cited by 126 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
126citing papers in PubMed, 3 pooled it
14.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02848651 phase2completednot on this map

A Phase II Single-Arm Study of Atezolizumab Monotherapy in Locally Advanced or Metastatic Non-Small Cell Lung Cancer: Clinical Evaluation of Novel Blood-Based Diagnostics

TypeinterventionalSponsorGenentech, Inc.Ran2016 to 2019Enrolled153ConditionsNon-Small Cell Lung CancerArmsAtezolizumab
3 · Its place in the literature

Who cites it

126 citing papers in PubMed, 3 syntheses or guidelines pooled it, 162 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Trial
  5. TAPISTRY: A Phase II Study of Atezolizumab in Patients with Tumor Mutational Burden-High Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Trial
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  11. Review
  12. Article
  13. Applications of circulating tumor DNA in unresectable and advanced non-small cell lung cancer immunotherapy: from stratification to therapeutic guidance.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Observational
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66 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 11 institutions in 2 countries.

Edward S Kim *City of Hope National Medical Center, Los Angeles, CA, USA.
Vamsidhar Velcheti *Cleveland Clinic, Cleveland, OH, USA. vamsidhar.velcheti@nyulangone.org.ORCID http://orcid.org/0000-0002-6589-0759
Tarek MekhailAdventHealth Cancer Institute, Orlando, FL, USA.
Cindy YunGenentech, Inc., South San Francisco, CA, USA.
Sarah M ShaganGenentech, Inc., South San Francisco, CA, USA.
Sylvia HuGenentech, Inc., South San Francisco, CA, USA.
Young Kwang ChaeNorthwestern University Feinberg School of Medicine, Chicago, IL, USA.
Ticiana A LealSchool of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
Jonathan E DowellDepartment of Medicine, Veterans Affairs North Texas Healthcare System, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Michaela L TsaiMinnesota Oncology, Minneapolis Clinic, Minneapolis, MN, USA.
Christopher S R DakhilCancer Center of Kansas, Wichita, KS, USA.
Philip StellaSt. Joseph Mercy Hospital, Ann Arbor, MI, USA.
Yanling JinF. Hoffmann-La Roche, Ltd, Mississauga ON, Canada.
David S ShamesGenentech, Inc., South San Francisco, CA, USA.
Erica SchleifmanGenentech, Inc., South San Francisco, CA, USA.
David A FabrizioFoundation Medicine, Inc, Cambridge, MA, USA.
See PhanGenentech, Inc., South San Francisco, CA, USA.
Mark A SocinskiAdventHealth Cancer Institute, Orlando, FL, USA.
Florida Hospital Cancer Institute · USCancer Center of Kansas · USCity Of Hope National Medical Center · USCleveland Clinic · USFoundation Medicine (United States)Minnesota Oncology · USNorthwestern University · USRoche (Canada) · CASouthwestern Medical Center · USTrinity Health Ann Arbor Hospital · USUniversity of Wisconsin–Madison · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Tumor mutational burden (TMB) in circulating tumor DNA (ctDNA) has shown promise in predicting benefit from PD-L1/PD-1 inhibitors in retrospective studies. Aiming to assess blood TMB (bTMB) prospectively, we conducted B-F1RST ( NCT02848651 ), an open-label, phase 2 trial that evaluated bTMB as a predictive biomarker for first-line atezolizumab monotherapy in locally advanced or metastatic stage IIIB-IVB non-small cell lung cancer (n = 152). The co-primary endpoints were investigator-assessed objective response rate (ORR) per RECIST version 1.1 and investigator-assessed progression-free survival (PFS) between high and low bTMB subgroups at the pre-defined bTMB ≥ 16 (14.5 mutations per megabase) cutoff. Secondary endpoints included investigator-assessed PFS, overall survival (OS) and duration of response at various bTMB cutoffs, as well as safety. Investigator-assessed PFS in the bTMB ≥ 16 versus bTMB < 16 groups was not statistically significant. However, bTMB ≥ 16 was associated with higher ORR, and ORR improved as bTMB cutoffs increased. No new safety signals were seen. In exploratory analyses, patients with maximum somatic allele frequency (MSAF) < 1% had higher ORR than patients with MSAF ≥ 1%. However, further analysis showed that this effect was driven by better baseline prognostics rather than by MSAF itself. At 36.5-month follow-up, an exploratory analysis of OS found that bTMB ≥ 16 was associated with longer OS than bTMB < 16. Further study and assay optimization will be required to develop bTMB as a predictive, standalone biomarker of immunotherapy or for use in conjunction with other biomarkers.

Indexed as

Carcinoma, Non-Small-Cell LungCirculating Tumor DNALung NeoplasmsAntibodies, Monoclonal, HumanizedBiomarkers, TumorHumansImmune Checkpoint InhibitorsMutationRetrospective StudiesAntibodies, Monoclonal, HumanizedatezolizumabBiomarkers, TumorCirculating Tumor DNAImmune Checkpoint Inhibitors

Identifiers

PMID35422531
PMCPMC9117143
OpenAlexW4224035333

What OpenQuestion holds

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LicenceCC BY
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.