{"entity":{"id":"idea-bio1-molecular-progression-add-on","kind":"idea","name":"Add a drug when the blood test turns, without stopping the one that works","aka":[],"tldr":"When a resistance mutation first appears in the blood, the current drug is often still controlling most of the tumour. Adding a second drug rather than swapping may keep both under control.","summary":"Most ctDNA-guided strategies switch therapy at molecular progression. Because the resistant clone is usually a minority at that point, switching abandons control of the sensitive majority. An additive strategy keeps the backbone and adds a mechanism-matched agent when a specific resistance alteration crosses a threshold in plasma, with the aim of suppressing both populations.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Acquired resistance to every therapy): Soria et al., Osimertinib in untreated EGFR-mutated NSCLC (FLAURA, NEJM 2018)","url":"https://doi.org/10.1056/NEJMoa1713137"}],"tags":[],"related":["idea-ctdna-switch-generalised"],"cancers":["nsclc"],"sections":[],"technologies":["liquid-biopsy"],"targets":["met","egfr"],"drugs":["osimertinib","amivantamab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-resistance","b-trial-design"],"keyPapers":["paper-flaura-nejm-2018","paper-osimertinib-nsclc-n-engl-j-med-2017","paper-osimertinib-nsclc-n-engl-j-med-2020"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Mechanism-matched addition at molecular progression yields longer time to radiographic progression than either continuing alone or switching, in patients with a single dominant emergent mechanism.","rationale":"Combination at the point of minimal resistant burden is when the added agent has the best chance of eradicating the emergent clone, and the backbone still suppresses the dominant population.","test":"Three-arm randomised phase 2 at molecular progression on osimertinib with detectable MET amplification: continue, switch, or add a MET inhibitor; primary endpoint time to radiographic progression.","maturity":"speculative","actor":"clinic","cost":"medium","horizonYears":5},"route":"/ideas/idea-bio1-molecular-progression-add-on/","neighbours":{"idea":[{"id":"idea-ctdna-switch-generalised","kind":"idea","name":"Molecular-progression switching beyond ESR1","route":"/ideas/idea-ctdna-switch-generalised/"}],"cancer":[{"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/"}],"target":[{"id":"egfr","kind":"target","name":"EGFR","route":"/targets/egfr/"},{"id":"met","kind":"target","name":"MET","route":"/targets/met/"}],"drug":[{"id":"amivantamab","kind":"drug","name":"Amivantamab","route":"/drugs/amivantamab/"},{"id":"osimertinib","kind":"drug","name":"Osimertinib","route":"/drugs/osimertinib/"}],"bottleneck":[{"id":"b-resistance","kind":"bottleneck","name":"Acquired resistance to every therapy","route":"/bottlenecks/b-resistance/"},{"id":"b-trial-design","kind":"bottleneck","name":"Trial design, endpoints and cost","route":"/bottlenecks/b-trial-design/"}],"paper":[{"id":"paper-flaura-nejm-2018","kind":"paper","name":"FLAURA: osimertinib as first treatment for EGFR-mutated lung cancer","route":"/key-papers/paper-flaura-nejm-2018/"},{"id":"paper-osimertinib-nsclc-n-engl-j-med-2017","kind":"paper","name":"Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer","route":"/key-papers/paper-osimertinib-nsclc-n-engl-j-med-2017/"},{"id":"paper-osimertinib-nsclc-n-engl-j-med-2020","kind":"paper","name":"Overall Survival with Osimertinib in Untreated, EGFR -Mutated Advanced NSCLC","route":"/key-papers/paper-osimertinib-nsclc-n-engl-j-med-2020/"}]}}