{"entity":{"id":"paper-gandara-blood-tmb-atezolizumab-nat-med-2018","kind":"paper","name":"Blood-based tumor mutational burden as a predictor of clinical benefit in non-small-cell lung cancer patients treated with atezolizumab","aka":[],"tldr":"Counting mutations in a blood sample rather than in a piece of tumour identified the patients who gained most from one immunotherapy drug, which matters because many patients with advanced lung cancer have no tissue left to test.","summary":"A blood-based assay to measure tumour mutational burden in plasma was developed and evaluated retrospectively in two large randomised trials used as test and validation studies. The assay is technically distinct from tissue-based approaches. High blood-based burden reproducibly identified patients who derived clinically significant improvements in progression-free survival from atezolizumab in second-line and later non-small-cell lung cancer.","asOf":"2026-09-25","links":[{"label":"Gandara et al., Nat Med 2018: blood-based tumour mutational burden as a predictor of atezolizumab benefit","url":"https://doi.org/10.1038/s41591-018-0134-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30082870/"}],"tags":[],"related":["tmb-high"],"cancers":["nsclc"],"sections":[],"technologies":["liquid-biopsy","tmb-testing","checkpoint-inhibitor"],"targets":["pdl1"],"drugs":["atezolizumab"],"companies":[],"institutions":[],"pathways":["pd1-checkpoint"],"terms":["tmb","ctdna","cfdna"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2018,"doi":"10.1038/s41591-018-0134-3","pmid":"30082870","authors":"Gandara DR, Paul SM, Kowanetz M, et al.","paperType":"translational","findings":["A plasma assay can estimate tumour mutational burden without tissue.","High blood-based burden identified atezolizumab benefit in test and validation trials.","Blood-based and tissue-based burden are distinct measurements with distinct thresholds."],"whatItMeans":"It answered the tissue-exhaustion problem for one biomarker, and in doing so added a third unit to a measurement that already had two, which is part of why the field never converged on a threshold.","caveats":["Retrospective analyses of trials not designed for the question.","Blood-based burden depends on tumour shedding, so low-shedding tumours are unclassifiable.","The prospective randomised test of a blood-based threshold did not confirm a treatment benefit."],"changedPractice":false},"route":"/key-papers/paper-gandara-blood-tmb-atezolizumab-nat-med-2018/","neighbours":{"biomarker":[{"id":"tmb-high","kind":"biomarker","name":"TMB-high (tumour mutational burden >= 10 mutations per megabase)","route":"/biomarkers/tmb-high/"}],"cancer":[{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"},{"id":"tmb-testing","kind":"technology","name":"Tumour mutational burden testing","route":"/technologies/tmb-testing/"}],"target":[{"id":"pdl1","kind":"target","name":"PD-L1","route":"/targets/pdl1/"}],"drug":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"}],"pathway":[{"id":"pd1-checkpoint","kind":"pathway","name":"PD-1 / PD-L1 immune checkpoint & T-cell activation","route":"/pathways/pd1-checkpoint/"}],"term":[{"id":"cfdna","kind":"term","name":"Cell-free DNA (cfDNA)","route":"/terms/cfdna/"},{"id":"ctdna","kind":"term","name":"Circulating tumour DNA (ctDNA)","route":"/terms/ctdna/"},{"id":"tmb","kind":"term","name":"Tumour mutational burden (TMB)","route":"/terms/tmb/"}],"journal":[{"id":"nature-medicine","kind":"journal","name":"Nature Medicine","route":"/journals/nature-medicine/"}]}}