{"entity":{"id":"idea-tr1-immunotherapy-stop-trials","kind":"idea","name":"Randomised trials of stopping immunotherapy after one year versus continuing","aka":[],"tldr":"Immunotherapy is often given for two years or until it stops working, but responses can last long after stopping. Trials that randomly assign responders to stop or continue would show whether the extra year is needed.","summary":"Non-inferiority trials randomising patients with response or stable disease after 12 months of PD-1/PD-L1 therapy to discontinuation with surveillance and retreatment at progression versus continuation to 24 months or beyond, with a 'treatment-free interval' and cumulative drug exposure as secondary endpoints. Several academic trials (e.g., in melanoma and NSCLC) are under way; the proposal is to make stop-versus-continue a standard post-approval requirement for durable-response agents.","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":["melanoma","nsclc"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":["pd1","pdl1"],"drugs":["pembrolizumab","nivolumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["checkmate-227","checkmate-915","fianlimab-phase3-melanoma","keynote-042","relativity-098"],"people":[],"bottlenecks":["b-trial-design","b-drug-pricing","b-toxicity-qol"],"keyPapers":["paper-davis-bmj","paper-topalian-anti-pd1-nejm-2012","paper-keynote-024-nejm-2016","paper-keynote-010-lancet-2016"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Stopping at 12 months in responders is non-inferior for OS with substantially lower cumulative toxicity and cost, and retreatment at progression recovers response in a meaningful fraction.","rationale":"Long-term follow-up of early checkpoint trials shows durable responses persisting for years after treatment ended; pharmacology suggests receptor occupancy persists for months.","test":"Pool the ongoing academic stop trials in a prospective meta-analysis with a pre-agreed non-inferiority margin; require sponsors of new checkpoint approvals to contribute to a duration trial.","maturity":"being-tested-at-scale","actor":"research","cost":"medium","horizonYears":4},"route":"/ideas/idea-tr1-immunotherapy-stop-trials/","neighbours":{"cancer":[{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"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/"}],"target":[{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"},{"id":"pdl1","kind":"target","name":"PD-L1","route":"/targets/pdl1/"}],"drug":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"trial":[{"id":"checkmate-227","kind":"trial","name":"CheckMate 227","route":"/trials/checkmate-227/"},{"id":"checkmate-915","kind":"trial","name":"CheckMate 915","route":"/trials/checkmate-915/"},{"id":"fianlimab-phase3-melanoma","kind":"trial","name":"Fianlimab + cemiplimab phase 3 (first-line melanoma)","route":"/trials/fianlimab-phase3-melanoma/"},{"id":"keynote-042","kind":"trial","name":"KEYNOTE-042","route":"/trials/keynote-042/"},{"id":"relativity-098","kind":"trial","name":"RELATIVITY-098","route":"/trials/relativity-098/"}],"bottleneck":[{"id":"b-drug-pricing","kind":"bottleneck","name":"Prices and value","route":"/bottlenecks/b-drug-pricing/"},{"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/"},{"id":"paper-keynote-010-lancet-2016","kind":"paper","name":"KEYNOTE-010 (Herbst 2016): pembrolizumab versus docetaxel in previously treated PD-L1-positive lung cancer","route":"/key-papers/paper-keynote-010-lancet-2016/"},{"id":"paper-keynote-024-nejm-2016","kind":"paper","name":"KEYNOTE-024: pembrolizumab alone beats chemotherapy in PD-L1-high lung cancer","route":"/key-papers/paper-keynote-024-nejm-2016/"},{"id":"paper-topalian-anti-pd1-nejm-2012","kind":"paper","name":"Topalian 2012: the first large trial of a PD-1 antibody shows durable responses across melanoma, lung and kidney cancer","route":"/key-papers/paper-topalian-anti-pd1-nejm-2012/"}]}}