ideasIdea
ctDNA-guided duration of PARP maintenance
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.
Two years (SOLO-1) or three years (PRIMA) of maintenance are arbitrary. Serial ctDNA could individualise duration and detect BRCA reversion mutations, the main resistance mechanism, months before imaging relapse.
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.
What would test it
Randomised de-escalation trial with tumour-informed ctDNA at 12 months; primary endpoint 3-year PFS non-inferiority.
Maturity
speculative
Pages like this
not linked directly; found by shared links- PersonAmit M. Oza
Shares Niraparib, Olaparib, Ovarian cancer.
- TermMaintenance therapy
Shares Niraparib, PARP inhibitors, Olaparib, Ovarian cancer.
- PairingPARP inhibitor + AR pathway inhibitor (prostate)
Shares Niraparib, PARP inhibitors, Olaparib.
- PersonAlan Ashworth
Shares PARP inhibitors, Olaparib, Ovarian cancer.
- InstitutionARCAGY-GINECO
Shares Niraparib, PARP inhibitors, Olaparib, Ovarian cancer.
- IdeaA functional test for homologous recombination deficiency validated across laboratories
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- IdeaStart low and step up: individualised titration of oral cancer drugs, randomised
Shares Niraparib, PARP inhibitors.
- InstitutionStephenson Cancer Center, OU Health
Shares PARP inhibitors, Olaparib, Ovarian cancer.