{"entity":{"id":"idea-tr1-ctdna-guided-stop-in-metastatic-disease","kind":"idea","name":"Use tumour DNA in blood to decide when to pause treatment in metastatic cancer","aka":[],"tldr":"If a blood test shows no tumour DNA after months of treatment, a trial could test pausing the drug and restarting only when the DNA reappears, giving patients time off without waiting for scans to show growth.","summary":"Randomised trials in metastatic disease where patients with sustained ctDNA clearance on therapy are allocated to continued treatment or a monitored treatment holiday with ctDNA-triggered resumption. Endpoints: time to treatment failure, time on treatment, QoL, OS non-inferiority. Distinct from adjuvant ctDNA-guided escalation (DYNAMIC, IMvigor011), this addresses de-escalation in the palliative setting where lead time over imaging gives a safety margin.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trial design, endpoints and cost): Davis et al., Availability of evidence of benefits on survival and quality of life of cancer drugs approved by EMA 2009-13 (BMJ 2017)","url":"https://doi.org/10.1136/bmj.j4530"}],"tags":[],"related":[],"cancers":["colorectal","nsclc"],"sections":[],"technologies":["liquid-biopsy","mrd-testing"],"targets":[],"drugs":[],"companies":["natera","guardant-health"],"institutions":[],"pathways":[],"terms":["ctdna"],"trials":["dynamic","imvigor011"],"people":[],"bottlenecks":["b-trial-design","b-toxicity-qol"],"keyPapers":["paper-davis-bmj"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"ctDNA-guided holidays in responders will reduce time on drug by at least a third with non-inferior OS and better QoL, and molecular relapse will be detected before clinical deterioration in the large majority.","rationale":"ctDNA falls precede radiographic response and molecular relapse precedes radiographic progression by months in several tumour types. Intermittent strategies in colorectal cancer (chemotherapy holidays) were safe when guided by clinical criteria alone.","test":"Run a phase 2/3 trial in a ctDNA-shedding cancer (colorectal or lung) randomising sustained-clearance patients to holiday vs continuation, with pre-specified non-inferiority on OS at two years.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":4},"route":"/ideas/idea-tr1-ctdna-guided-stop-in-metastatic-disease/","neighbours":{"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"technology":[{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"},{"id":"mrd-testing","kind":"technology","name":"MRD / molecular residual disease testing","route":"/technologies/mrd-testing/"}],"company":[{"id":"guardant-health","kind":"company","name":"Guardant Health","route":"/companies/guardant-health/"},{"id":"natera","kind":"company","name":"Natera","route":"/companies/natera/"}],"term":[{"id":"ctdna","kind":"term","name":"Circulating tumour DNA (ctDNA)","route":"/terms/ctdna/"}],"trial":[{"id":"dynamic","kind":"trial","name":"DYNAMIC","route":"/trials/dynamic/"},{"id":"imvigor011","kind":"trial","name":"IMvigor011","route":"/trials/imvigor011/"}],"bottleneck":[{"id":"b-toxicity-qol","kind":"bottleneck","name":"Toxicity and quality of life are undervalued","route":"/bottlenecks/b-toxicity-qol/"},{"id":"b-trial-design","kind":"bottleneck","name":"Trial design, endpoints and cost","route":"/bottlenecks/b-trial-design/"}],"paper":[{"id":"paper-davis-bmj","kind":"paper","name":"Availability of evidence of benefits on overall survival and quality of life of cancer drugs approved by European Medicines Agency: retrospective cohort study of drug approvals 2009-13","route":"/key-papers/paper-davis-bmj/"}]}}