By Ana Espino | Published on February 3, 2026 | 3 min read
Endometrial cancer is the most
common gynecologic cancer in industrialized countries and primarily affects
postmenopausal women. Its prevalence is increasing, mainly due to obesity and
an aging population. While early-stage disease is often curable through
surgery, advanced or recurrent forms have a poor prognosis, with a
5-year overall survival rate below 20%.
Treatment options for advanced
stages remain limited. Chemotherapy is the current standard, but its
effectiveness is moderate, and relapses are frequent. Targeted therapies, such
as immune checkpoint inhibitors, have shown benefit in select patients, yet no
personalized strategy is currently validated for most cases.
PARP inhibitors (poly-ADP ribose polymerase),
already effective in ovarian and breast cancers with BRCA mutations or
homologous recombination deficiency (HRD), are emerging as a promising avenue
in endometrial cancer—particularly for patients with TP53, ARID1A mutations,
or mismatch repair deficiency (MMRd).
In this context, this study was conducted to
evaluate the efficacy and safety of PARP inhibitors, used alone or in
combination, in patients with advanced or recurrent endometrial cancer.
Is PARP the answer for everyone?
A total of 11 studies
involving 503 patients, mostly phase II trials, were included. The PARP
inhibitors studied were olaparib, niraparib, rucaparib, and talazoparib,
administered either alone or in combination (e.g., with PD-1 inhibitors,
anti-VEGF therapies, etc.). The primary endpoints were objective
response rate (ORR), progression-free survival (PFS), disease
control rate (DCR), and treatment safety.
The ORR in monotherapy remained low
(~4%), except in patients with a positive HRD status or specific
mutations (p53abn, BRCA1/2), where it increased to 11–15%. In
combination therapies, the ORR rose to 26% in certain subgroups,
particularly those receiving immune checkpoint inhibitors.
Disease control was more favorable
in MMRd patients or those with alterations in DNA repair genes,
suggesting increased sensitivity to the genotoxic stress induced by PARP
inhibitors. Median PFS ranged from 2.5 to 8.3 months, depending on the
treatment combination and molecular profile.
In terms of safety, adverse effects were
generally manageable, with hematologic events (anemia, neutropenia) and digestive
symptoms (nausea, fatigue) being the most common, and rarely of grade 3
or higher.
Targeted… but not yet for all
Advanced endometrial cancer is a
common and aggressive disease, often diagnosed at a stage when treatment
options are limited. The main challenge remains the lack of effective
targeted therapies for most patients, despite progress in tumor molecular
profiling.
This study aimed to assess the role
of PARP inhibitors, alone or in combination, in advanced or relapsed
patients. The findings suggest modest benefits in monotherapy, but promising
results in specific molecular subgroups (HRD+, MMRd, TP53 or BRCA
mutations), particularly when combined with other targeted or immunotherapies.
However, several limitations remain and call for further
research. Larger and better-controlled clinical trials are needed, as well as
improved identification of genetic profiles and standardization of HRD
testing. Future studies should also explore predictive biomarkers of
treatment response and the most effective combination regimens. Lastly,
long-term effects and impact on quality of life must be evaluated to truly
integrate these therapies into personalized clinical practice.
Read next: Folate intake and the risk of endometrial cancer: a dose-response meta-analysis
About the author – Ana EspinoPhD in Immunology, specialized in Virology
As a scientific writer, Ana is passionate about bridging the gap between research and real-world impact. With expertise in immunology, virology, oncology, and clinical studies, she makes complex science clear and accessible. Her mission: to accelerate knowledge sharing and empower evidence-based decisions through impactful communication.
