{"entity":{"id":"idea-ctdna-guided-parp-duration","kind":"idea","name":"ctDNA-guided duration of PARP maintenance","aka":[],"tldr":"Stop PARP inhibitors early in women whose blood shows no residual tumour DNA, and extend or switch in those whose ctDNA persists or reverts BRCA.","summary":"The two-year duration of olaparib maintenance in SOLO-1 and the three-year duration of niraparib in PRIMA were set by trial design rather than biology, so this idea proposes letting serial ctDNA decide how long each woman with ovarian cancer stays on a PARP inhibitor. Patients who are ctDNA-negative at twelve months would stop, while those with persistent ctDNA or a BRCA reversion mutation in plasma would switch to an ATR or POLQ inhibitor before radiographic progression. The rationale is that MRD-guided de-escalation has been shown in DYNAMIC and IMvigor011, and that BRCA reversion, the main resistance mechanism, is detectable in blood months before imaging relapse. The proposed test is a randomised de-escalation trial with tumour-informed ctDNA, and the idea remains speculative.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT01844986: SOLO-1","url":"https://clinicaltrials.gov/study/NCT01844986"},{"label":"ClinicalTrials.gov NCT02655016: PRIMA / ENGOT-OV26","url":"https://clinicaltrials.gov/study/NCT02655016"}],"tags":[],"related":[],"cancers":["ovarian"],"sections":[],"technologies":["mrd-testing","parp-inhibitor"],"targets":[],"drugs":["olaparib","niraparib"],"companies":[],"institutions":[],"pathways":[],"terms":["mrd"],"trials":["solo-1","prima"],"people":[],"bottlenecks":[],"keyPapers":["paper-solo-1-nejm-2018","paper-niraparib-ovarian-n-engl-j-med-2016","paper-prima-niraparib-nejm-2019"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"ctDNA-negative patients at 12 months can stop PARP maintenance without loss of PFS; ctDNA-positive patients benefit from switching to an ATR or POLQ inhibitor before radiographic progression.","rationale":"MRD-guided de-escalation is proven in colon cancer (DYNAMIC) and bladder (IMvigor011); BRCA reversion is detectable in plasma.","test":"Randomised de-escalation trial with tumour-informed ctDNA at 12 months; primary endpoint 3-year PFS non-inferiority.","maturity":"speculative"},"route":"/ideas/idea-ctdna-guided-parp-duration/","neighbours":{"cancer":[{"id":"ovarian","kind":"cancer","name":"Ovarian cancer","route":"/cancers/ovarian/"},{"id":"platinum-sensitive-ovarian-cancer","kind":"cancer","name":"Platinum-sensitive ovarian cancer","route":"/cancers/platinum-sensitive-ovarian-cancer/"}],"technology":[{"id":"mrd-testing","kind":"technology","name":"MRD / molecular residual disease testing","route":"/technologies/mrd-testing/"},{"id":"parp-inhibitor","kind":"technology","name":"PARP inhibitors","route":"/technologies/parp-inhibitor/"}],"drug":[{"id":"niraparib","kind":"drug","name":"Niraparib","route":"/drugs/niraparib/"},{"id":"olaparib","kind":"drug","name":"Olaparib","route":"/drugs/olaparib/"}],"term":[{"id":"mrd","kind":"term","name":"Minimal / molecular residual disease (MRD)","route":"/terms/mrd/"}],"trial":[{"id":"prima","kind":"trial","name":"PRIMA / ENGOT-OV26","route":"/trials/prima/"},{"id":"solo-1","kind":"trial","name":"SOLO-1","route":"/trials/solo-1/"}],"paper":[{"id":"paper-niraparib-ovarian-n-engl-j-med-2016","kind":"paper","name":"Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer","route":"/key-papers/paper-niraparib-ovarian-n-engl-j-med-2016/"},{"id":"paper-prima-niraparib-nejm-2019","kind":"paper","name":"PRIMA: niraparib maintenance in newly diagnosed advanced ovarian cancer","route":"/key-papers/paper-prima-niraparib-nejm-2019/"},{"id":"paper-solo-1-nejm-2018","kind":"paper","name":"SOLO-1: two years of olaparib maintenance after first-line chemotherapy for BRCA-mutated ovarian cancer","route":"/key-papers/paper-solo-1-nejm-2018/"}]}}