PARP inhibitors show favorable long-term results in patients with recurrent ovarian cancer.

Scientific Culture and Innovation Unit

An international and multicenter study in which the Puerta de Hierro Hospital participates, published in JAMA Oncology, It analyzes the long-term evolution of patients with recurrent ovarian cancer who achieved an exceptional response to PARP inhibitors.

Photo of the Puerta de Hierro University Hospital in Majadahonda. Image gallery of the hospital.

In Spain, ovarian cancer is one of the most common gynecological tumors and constitutes the main cause of death from gynecologic cancer, largely due to the fact that most are diagnosed at advanced stages, due to the difficulty in detecting it early. Treatment usually combines surgery to remove as much of the tumor as possible with chemotherapy. However, in the years following treatment, recurrence is common, which makes maintenance therapies play a fundamental role. Among them are PARP inhibitors, which have represented a paradigm shift in the treatment of advanced ovarian cancer.

Dr. Constanza Maximiano, oncologist at the Puerta de Hierro-Majadahonda University Hospital and member of the Spanish Group for Research in Gynecological Cancer (GEICO), has participated in this international study developed in 41 centers in 14 countries that analyzes the long-term effects of PARP inhibitors. The results show that the majority of patients remained free of disease progression for years, even among those who discontinued treatment without the disease progressing, and point to new questions about the optimal duration of this therapy.

Long-term effects of PARP inhibitors

PARP inhibitors are a new class of drugs that act by eliminating tumor cells, helping to control the disease. However, there was uncertainty about the duration of treatment, the risk of tumor recurrence, and the effects of prolonged exposure. Until now, the standard strategy was to maintain treatment until the progression of the disease or until the occurrence of adverse effects that necessitated its discontinuation.

The researchers analyzed the results of 320 patients with an exceptional response to these drugs, defined as the absence of disease progression for five years or more since the start of treatment. The results showed that the rate of progression-free survival -or the time during which patients remain without disease progression- at 10 years was 78.7%, while the overall survival rate reached 90.5%. 

In addition, only 34 patients experienced disease progression at 5 years or more since the start of treatment; the last progression was recorded in a patient at 14.8 years since the start of treatment.

Another objective of this work was the analysis of the long-term safety profile of PARP inhibitors, especially in relation to certain serious hematological complications, such as myelodysplastic syndrome and acute myeloid leukemia. In the study, a low incidence of these adverse effects was observed, identifying five cases (1.6 %) of myelodysplastic syndrome or acute myeloid leukemia. Therefore, although the risk of these effects is low, further studies are still necessary.

Duration of treatment

Of the 320 patients included in the study, 211 received continuous treatment with PARP inhibitors, while 109 discontinued it due to medical recommendations, progression of the disease, toxic effects, or patient preferences. Among the 85 patients who discontinued treatment for reasons other than progression, the 10-year progression-free survival was 90.1%, compared with 72.5% among those who continued treatment. These results suggest that some patients with an exceptional response may maintain disease control after discontinuing treatment. Therefore, the possibility of discontinuing treatment is proposed in these cases, without evidence of disease progression, which implies a paradigm shift from the currently recommended indefinite treatment.

The work also aimed to identify the genetic characteristics that could be associated with this exceptional response to PARP inhibitors. The researchers observed that 73% of the patients had mutations in the genes BRCA1 y BRCA2, These data suggest that the presence of some mutations in these genes could be associated with this exceptional response. However, the authors note that further studies are needed to identify which patients could benefit from an interruption of treatment strategy.

Towards a more personalized treatment strategy

This work provides new evidence on the long-term treatment of advanced ovarian cancer with PARP inhibitors. Most patients with exceptional response to PARP inhibitors remained disease-free, including those who discontinued treatment without the disease progressing. Although the researchers consider further studies necessary, these data may contribute to advancing towards increasingly personalized therapeutic strategies that allow tailoring the duration of treatment for each patient.

References: Haggstrom, L., Lee, Y. C., Barretina-Ginesta, M. P., Jaeger, A., Woelber, L., Woopen, H., … & Friedlander, M. (2026). Long-term outcomes in patients with recurrent ovarian cancer and exceptional response to PARP inhibitors. JAMA oncology, 12(8), 845–854. https://doi.org/10.1001/jamaoncol.2026.1924