TOPLINE

Patients with platinum-sensitive recurrent ovarian cancer who achieved exceptional responses to maintenance poly(ADP‐ribose) polymerase (PARP) inhibitors demonstrated durable long-term outcomes, with 10-year progression-free survival (PFS) approaching 79% and 10-year overall survival exceeding 90% in a large international cohort. Among this population, patients who discontinued PARP inhibitors for reasons other than disease progression — generally those with more durable responses — had similar or numerically higher PFS than those who remained on therapy, though findings are limited by retrospective design and nonrandom treatment decisions.

METHODOLOGY

• A subset of patients with platinum-sensitive recurrent ovarian cancer who receive maintenance PARP inhibitors have exceptional response. Although the recommendation is to continue PARP inhibitors until progression or unacceptable toxic effects, the optimal duration of PARP inhibitors, and the risks for late progression or myelodysplastic syndrome/acute myeloid leukemia (AML) in patients with exceptional response are unknown.
• To assess the long-term outcomes in this patient population, researchers conducted an international, multicenter, retrospective cohort study across 41 sites in 14 countries from January 11, 2023, to November 10, 2025. The study included 320 patients with platinum-sensitive recurrent ovarian cancer who had exceptional response to maintenance PARP inhibitors, defined as PFS of 5 years or more after starting the drugs.
• The median PARP inhibitor duration was 75.0 months, with 211 patients (65.9%) receiving continuous PARP inhibitors and 109 (34%) discontinuing for various reasons including physician recommendation (34 patients), disease progression beyond 5 years (24 patients), toxic effects (22 patients), patient preference (17 patients), or other reasons (12 patients).
• The primary endpoint was PFS, defined as time from PARP inhibitor initiation to progressive disease or death, and secondary endpoints included overall survival and toxic effects, such as incidence of myelodysplastic syndrome or AML. The study included genetic analyses of BRCA1/2 variant status as well.

TAKEAWAY

• In this population of exceptional responders, the 7.5-year PFS rate was 88.8% and the 10-year PFS rate was 78.7%, with a 10-year overall survival rate of 90.5%.
• Patients who discontinued PARP inhibitors for reasons other than disease progression (26.6% or 85 patients) had a 10-year PFS of 90.1% compared to 72.5% for those who continued PARP inhibitors.
• Overall, 34 patients (10.6%) developed disease progression at or after 5 years: 24 while taking PARP inhibitors and 6 after discontinuing. As for toxic effects, myelodysplastic syndrome or AML occurred in 5 patients (1.6%).
• The only baseline characteristic associated with prolonged PFS was a long interval between initial diagnosis and recurrence (≥ 18 months; hazard ratio, 0.28; P < .001), whereas no difference in PFS was observed based on BRCA1/2 status, PARP inhibitor duration, or type of BRCA1/2 variant.

IN PRACTICE

In this cohort study, many patients with exceptional response to PARP inhibitors remained progression free, including most who discontinued PARP inhibitors without progression, the authors wrote, adding that the risk of myelodysplastic syndrome/AML was low. The authors concluded that “these results can guide counseling on the duration of maintenance PARP inhibitors in patients with exceptional response.”

SOURCE

The study, led by Lucy Haggstrom, MD, and Michael Friedlander, MBChB(Hons), PhD, both from Prince of Wales Hospital and the Royal Hospital for Women, Sydney, Australia, was published online on June 25 in JAMA Oncology.

LIMITATIONS

Patients with exceptional response represent the tail of the survival distribution in clinical trials, making a prospective study impractical, and the retrospective analysis carries a risk for selection bias, though sites were asked to contribute all eligible patients to minimize this risk. Genomic data were incomplete for some patients due to site-level privacy restrictions and missing data. The study was not powered to identify predictive factors for benefit from continued versus fixed-duration PARP inhibition. Researchers compared genetic characteristics against patients with ovarian cancer treated with maintenance PARP inhibitors in the first-line setting, as no suitable data were available for comparison with a typical population. No details were collected regarding the timing or extent of dose reductions or on the proportion who underwent risk-reducing bilateral mastectomy.

DISCLOSURES

Haggstrom disclosed receiving personal fees from Syndax Pharmaceuticals and nonfinancial support from Pfizer, Breast Cancer Trials, and the European Society For Medical Oncology outside the submitted work. Friedlander disclosed receiving grants from AstraZeneca and Novartis, as well as personal fees from AstraZeneca, AbbVie, BioNTech, MSD, ImmunoGen, and GSK outside the submitted work. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.