Long-Term Outcomes in Patients With Recurrent Ovarian Cancer and Exceptional Response to PARP Inhibitors
Lucy Haggstrom, Yeh Chen Lee, Maria-Pilar Barretina-Ginesta, Anna Jaeger, Linn Woelber, Hannah Woopen, Madeline Rhind, Jean-Sébastien Frenel, Aanum Aanum, Katharina Bischof, Marta Mongillo, Allison L. Brodsky, Jonathan Ledermann, Talayeh S. Ghezelayagh, Ingrid Boere, Sabrina Kaiser, Constanza Maximiano, Ora Rosengarten, Tamar Safra, Ana Pertejo, Sabrina Cecere, Isabelle Ray-Coquard, Stephanie Lheureux, Ros Glasspool, Marta Gil-Martin, Laura Tookman, Se Ik Kim, Suzana Mittelstadt, Miguel Corbellas Aparicio, Isabel Palacio, Cristina Martin-Lorente, Rebecca Kristeleit, Helena de la Cueva, Nelleke Ottevanger, Maria Quindós Varela, Hiroyuki Yoshida, Theresa Link, Lydia Gaba, Gloria Marquina, Nikki Burdett, Paul Johannet, Juliane Reichenbach, Tjoung-Won Park-Simon, Philip H. Klecker, Antonio González-Martín, Christian Marth, Clemens Liebrich, Levan Dzotsenidze, Sabine Heublein, Lawrence Kasherman, Cristina Perez, Maria Masvidal, Pau Guillén Sentís, Nikolaus de Gregorio, Franziska Hemptenmacher, Felix Hilpert, Jalid Sehouli, Clare Scott, Katherine Mary Tucker, Jack Dong, Cristina Fortuno, Amanda B. Spurdle, Michael Friedlander, , Susan Ellard, Anna Tinker, Andrew Clamp, Iain McNeish, Nicoletta Colombo, Sandro Pignata, Kristina Lindemann, Patricia Roxburgh, Jae-Weon Kim, Shannon Westin, Jonathan Berek, William Tew, Carol Aghajanian, Philipp HarterImportance
A subset of patients with platinum-sensitive recurrent ovarian cancer (PS-ROC) treated with maintenance poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors have exceptional response. Although licensing recommends continuing PARP inhibitors until progression or unacceptable toxic effects, the optimal duration of PARP inhibitors, and the risks of late progression, myelodysplastic syndrome (MDS), or acute myeloid leukemia (AML) in patients with exceptional response are unknown.
Objective
To determine the long-term outcomes of patients with PS-ROC who have exceptional response to PARP inhibitors, and to explore genotype-phenotype associations.
Design, Setting, and Participants
This was an international, multicenter, retrospective cohort study of patients with exceptional response to PARP inhibitors, defined as patients with PS-ROC and progression-free survival (PFS) of 5 years or longer from PARP inhibitor commencement. The study was conducted across 41 sites in 14 countries from January 11, 2023, to November 10, 2025.
Exposures
Treatment with PARP inhibitors.
Main Outcomes and Measures
The primary end point was PFS, and secondary end points included overall survival, toxic effects, and dose reductions.
Results
A total of 320 patients with exceptional response (mean [SD] age, 56.4 [9.4] years) were included, with a median follow-up of 6.8 years (95% CI, 6.6-7.0 years). The median (IQR) PARP inhibitor duration was 75.0 (64.0-91.0) months. Of patients with exceptional response, 211 (65.9%) received continuous PARP inhibitors, but 109 (34.1%) discontinued: 34 (10.6%) due to physician recommendation, 2 (7.5%) had disease progression beyond 5 years, 22 (6.9%) had toxic effects, 17 (5.3%) for patient preference, and 12 (3.8%) for another reason. The 7.5-year and 10-year PFS rates were 88.8% (95% CI, 84.5%-93.3%) and 78.7% (95% CI, 70.5%-87.9%), respectively. Among the patients, 85 (26.6%) discontinued PARP inhibitors for reasons other than disease progression, with a 10-year PFS of 90.1% (95% CI, 80.6%-100%) vs 72.5% (95% CI, 60.3%-87.2%) for those who continued taking PARP inhibitors. Five patients (1.6%) were diagnosed with late-onset MDS/AML. Patients with exceptional response were enriched for variants in the
Conclusions and Relevance
In this cohort study, most patients with exceptional response to PARP inhibitors remained progression free, including those who discontinued PARP inhibitors without progression. The risk of late-onset MDS/AML was low. These results can guide counseling on the duration of maintenance PARP inhibitors in patients with exceptional response and suggest that functional cure may be possible in patients with PS-ROC and exceptional response to PARP inhibitors.