2026-02-03
Endometrial cancer: Is PARP bringing new hope?
Gynecology
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.
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.
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.
About the author – Ana Espino
PhD 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.
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 Espino
PhD 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.
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