{"entity":{"id":"idea-ctdna-guided-adjuvant-melanoma","kind":"idea","name":"ctDNA-guided adjuvant therapy in stage II-III melanoma","aka":[],"tldr":"Most stage II patients never relapse, yet all are offered a year of immunotherapy. Use a blood test to treat only those with detectable residual disease.","summary":"The idea is to reserve adjuvant PD-1 therapy in stage II to III melanoma for patients with detectable residual disease on a tumour-informed ctDNA assay, or to start it when ctDNA appears, instead of treating everyone. KEYNOTE-716 and CheckMate 76K treat all stage IIB and IIC patients for a modest absolute benefit although most never relapse, so over-treatment and immune toxicity are substantial. Melanoma sheds ctDNA in proportion to burden, and IMvigor011 proved the concept of ctDNA-triggered adjuvant immunotherapy in bladder cancer. The hypothesis is equivalent distant metastasis-free survival with far fewer patients treated; the test is the UK DETECTION design of ctDNA-triggered versus standard adjuvant pembrolizumab, addressing the dormancy bottleneck.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT03553836: KEYNOTE-716","url":"https://clinicaltrials.gov/study/NCT03553836"},{"label":"ClinicalTrials.gov NCT04660344: IMvigor011","url":"https://clinicaltrials.gov/study/NCT04660344"}],"tags":[],"related":[],"cancers":["melanoma"],"sections":[],"technologies":["mrd-testing","checkpoint-inhibitor"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["mrd"],"trials":["keynote-716","imvigor011"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Reserving adjuvant PD-1 for ctDNA-positive patients (or starting at ctDNA conversion) achieves equivalent distant metastasis-free survival with far fewer patients treated.","rationale":"Melanoma sheds ctDNA proportional to burden; IMvigor011 proved the concept in bladder cancer; over-treatment and immune toxicity in stage II are substantial.","test":"Randomised trial of ctDNA-triggered versus standard adjuvant pembrolizumab in stage IIB-IIIA with DMFS endpoint (the DETECTION design).","maturity":"early-clinical"},"route":"/ideas/idea-ctdna-guided-adjuvant-melanoma/","neighbours":{"cancer":[{"id":"braf-v600-melanoma","kind":"cancer","name":"BRAF V600-mutant melanoma","route":"/cancers/braf-v600-melanoma/"},{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"id":"stage-ii-melanoma","kind":"cancer","name":"Stage IIB and IIC melanoma","route":"/cancers/stage-ii-melanoma/"},{"id":"stage-iii-melanoma","kind":"cancer","name":"Stage III melanoma (after surgery)","route":"/cancers/stage-iii-melanoma/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"mrd-testing","kind":"technology","name":"MRD / molecular residual disease testing","route":"/technologies/mrd-testing/"}],"term":[{"id":"mrd","kind":"term","name":"Minimal / molecular residual disease (MRD)","route":"/terms/mrd/"}],"trial":[{"id":"imvigor011","kind":"trial","name":"IMvigor011","route":"/trials/imvigor011/"},{"id":"keynote-716","kind":"trial","name":"KEYNOTE-716","route":"/trials/keynote-716/"}],"bottleneck":[{"id":"b-dormancy-mrd","kind":"bottleneck","name":"Dormant cells and minimal residual disease","route":"/bottlenecks/b-dormancy-mrd/"}]}}