Long-Term Outcomes in Patients With Recurrent Ovarian Cancer and Exceptional Response to PARP Inhibitors

Area of Science:

• Oncology
• Genetics
• Pharmacology

Background:

• A subset of patients with platinum-sensitive recurrent ovarian cancer (PS-ROC) exhibit exceptional response to maintenance poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors.
• Current guidelines recommend continuous PARP inhibitor treatment until disease progression or toxicity, but optimal duration for exceptional responders is unknown.
• The risks associated with prolonged PARP inhibitor use, including late progression and secondary malignancies like myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML), require investigation.

Purpose of the Study:

• To determine the long-term outcomes for patients with PS-ROC who achieve an exceptional response to PARP inhibitors.
• To explore potential genotype-phenotype associations in this patient subgroup.
• To evaluate the safety and efficacy of PARP inhibitor treatment duration in exceptional responders.

Main Methods:

• International, multicenter, retrospective cohort study involving 320 patients with exceptional response (defined as PS-ROC with ≥5 years progression-free survival on PARP inhibitors).
• Data collected from 41 sites across 14 countries.
• Primary endpoint: progression-free survival (PFS); Secondary endpoints: overall survival, toxic effects, and dose reductions.

Main Results:

• Median follow-up was 6.8 years; median PARP inhibitor duration was 75.0 months.
• 7.5-year and 10-year PFS rates were 88.8% and 78.7%, respectively.
• Discontinuation of PARP inhibitors without progression was associated with a 10-year PFS of 90.1%, compared to 72.5% for those continuing treatment; 1.6% of patients developed late-onset MDS/AML.

Conclusions:

• Most patients with exceptional response to PARP inhibitors maintained long-term PFS, including those who discontinued treatment without progression.
• The risk of late-onset MDS/AML in this cohort was low.
• Findings support counseling on PARP inhibitor duration for exceptional responders and suggest the possibility of functional cure in this patient population.