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

Importance: 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 BRCA1 RING domain and the BRCA2 DNA-binding domain. 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.

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Journal
JAMA Oncology
Published
2026-06-25
DOI
https://doi.org/10.1001/jamaoncol.2026.1924
Primary Topic
PARP inhibition in cancer therapy
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article
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article

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

Sabrina Kaiser, Constanza Maximiano, María Masvidal, P. Guillén Sentís et al.
JAMA Oncology
PARP inhibition in cancer therapy
article

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

Sabrina Kaiser, Constanza Maximiano, María Masvidal, P. Guillén Sentís, Katharina Bischof, Lydia Gaba, F Hemptenmacher, Allison L. Brodsky, I A Boere, A. Pertejo, Hannah Woopen, Juliane Reichenbach, Lawrence Kasherman, C Marth, Sabine Heublein, K Lindemann, Jack Dong, Tamar Safra, Cristina Fortuño, Cristina Martín-Lorente, Patricia Roxburgh, Talayeh Ghezelayagh, L Tookman, Yeh Chen Lee, Philipp Harter, Helena de la Cueva, Gloria Marquina, Dzotsenidze Ll, María Quindós Varela, N J COLOMBO, Jonathan Ledermann, Ros Glasspool, M L Friedlander, Clemens Liebrich, Madeline Rhind, L Haggström, Jae-Weon Kim, Susan Ellard, Jonathan Berek, Isabel Palacio, Anna Tinker, Iain McNeish, Nikki Burdett, Carol Aghajanian, Paul Johannet, William Tew, T Link, Clare Scott, Jalid Sehouli, Hiroyuki Yoshida, Ora Rosengarten, Tjoung-Won Park-Simon, Suzana Mittelstadt, Linn Woelber, Aanum Aanum, Anna Jaeger, Maria-Pilar Barretina-Ginesta, Jean-Sébastien Frenel, Amanda B. Spurdle, Shannon Westin, Cristina Perez, Philip H. Klecker, Sandro Pignata, Nelleke Ottevanger, Marta Mongillo, Katherine Mary Tucker, Nikolaus de Gregorio, Antonio González-Martín, Se Ik Kim, Stephanie Lheureux, Felix Hilpert, Andrew Clamp, Sabrina Cecere, Rebecca Kristeleit, Marta Gil-Martin, Miguel Corbellas Aparicio, Isabelle Ray-Coquard
article en

Abstract

Importance: 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 BRCA1 RING domain and the BRCA2 DNA-binding domain. 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.

JAMA Oncology
Université Claude Bernard Lyon 1 (FR), Gynecologic Oncology Group (US), Oslo University Hospital (NO), BC Cancer Agency (CA), University Health Network (CA), Memorial Sloan Kettering Cancer Center (US), Institut Català d'Ornitologia (ES), The University of Texas MD Anderson Cancer Center (US), Seoul National University (KR), Innsbruck Medical University (AT), Radboud University Nijmegen (NL), Universität Hamburg (DE), Tel Aviv University (IL), The University of Queensland (AU), The University of Melbourne (AU), Walter and Eliza Hall Institute of Medical Research (AU), Johannes Gutenberg University Mainz (DE), Guy's and St Thomas' NHS Foundation Trust (GB), QIMR Berghofer Medical Research Institute (AU), Tel Aviv Sourasky Medical Center (IL), Royal Hospital for Women (AU), Beatson West of Scotland Cancer Centre (GB), Peter MacCallum Cancer Centre (AU), Hospital Universitario La Paz (ES), Wollongong Hospital (AU), Hospital de Sant Pau (ES), Shaare Zedek Medical Center (IL), Princess Margaret Cancer Centre (CA), Radboud University Medical Center (NL), Hospital Clínico San Carlos (ES), UNSW Sydney (AU), Medizinische Hochschule Hannover (DE), Humboldt-Universität zu Berlin (DE), Arbeitsgemeinschaft Gynäkologische Onkologie Studiengruppe (DE), Institut de Recerca Biomèdica Catalunya Sud (ES), Hospital Universitario Puerta de Hierro Majadahonda (ES), Centre Léon Bérard (FR), Institut de Cancérologie de l'Ouest (FR), Institut Català d'Oncologia (ES), Klinik und Poliklinik für Psychosomatische Medizin und Psychotherapie (DE), University Medical Center Hamburg-Eppendorf (DE), Prince of Wales Hospital (AU), University Hospital Schleswig-Holstein (DE), Institut d'Investigació Biomèdica de Girona (ES), Klinik und Poliklinik für Frauenheilkunde und Fortpflanzungsmedizin (DE), Hospital Clínic de Barcelona (ES), Hospital Sant Pau i Santa Tecla (ES), Schweißtechnische Lehr- und Versuchsanstalt (DE), Leitat Technological Center (ES), Mammazentrum Hamburg (DE), Hospital Universitario Doctor Peset (ES), Saitama International Medical Center (JP), Hospital Universitario Central de Asturias (ES), The Christie NHS Foundation Trust (GB), Jena University Hospital (DE), Clinica Universidad de Navarra (ES), Fraunhofer Project Centre Wolfsburg (DE), Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" (IT), Kliniken Essen-Mitte (DE), CRUK Lung Cancer Centre of Excellence (GB), Nord-Ostdeutsche Gesellschaft für Gynäkologische Onkologie (DE), Erasmus MC Cancer Institute (NL), Spanish Ovarian Cancer Research Group (ES), University Hospital Ulm (DE), SLK-Kliniken Heilbronn (DE), Instituto de Investigación Biomédica de A Coruña (ES), University Hospital Carl Gustav Carus (DE), Krankenhaus Jerusalem (DE), University College London (GB), Imperial College London (GB), European Institute of Oncology (IT), Technische Universität Dresden (DE), Ludwig-Maximilians-Universität München (DE), Saitama Medical University (JP), University of Lübeck (DE), Stanford University (US)
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PARP inhibition in cancer therapy
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