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Updated: May 21, 2025
Evaluating the Angiogenetic Properties of Ovarian Cancer Stem-Like Cells using the Three-Dimensional Co-Culture System, NICO-1
Published on: December 5, 2020
Efficacy and Safety of Combination Therapy with PARP Inhibitors and Anti-Angiogenic Agents in Ovarian Cancer: A
István Baradács1,2, Brigitta Teutsch1,3,4, Ádám Vincze1,2
1Centre for Translational Medicine, Semmelweis University, 1085 Budapest, Hungary.
Abstract:
Introduction: Ovarian cancer is a significant contributor to gynecological cancer-related mortality, necessitating innovative treatment strategies. This systematic review and meta-analysis aimed to assess the efficacy and safety of combining PARP inhibitors with anti-angiogenic agents (AAAs) in the treatment of ovarian cancer. Methods: This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and was registered on PROSPERO (CRD42022319461). A systematic search of three electronic databases, including MEDLINE (via PubMed), EMBASE, and Cochrane Library was conducted to identify relevant randomized controlled trials (RCT) that evaluated the efficacy and safety of the combination therapy. Subgroup analyses were based on BRCA mutation status. Meta-analysis was conducted to estimate pooled hazard ratios (HR) and risk ratios (RR) for progression-free survival (PFS) and adverse events, respectively. The combination therapy was compared to PARP inhibitors alone and to chemotherapy. Heterogeneity was assessed using Higgins and Thompson's I2 statistic where applicable. Results: Seven RCTs involving 2397 patients were included. Combination therapy did not show a statistically significant improvement in PFS compared to PARP inhibitor monotherapy in the general population (HR 0.63, CI 0.37-1.06), or in BRCA-mutated (HR 0.70, CI 0.30-1.63) and BRCA wild-type subgroups (HR 0.39, CI 0.14-1.07). When compared to chemotherapy, combination therapy produced no significant PFS benefit in recurrent ovarian cancer (HR 0.83, CI 0.42-1.63) in the total population. Safety analysis revealed that hypertension and diarrhea were significantly more frequent in combination therapy compared with PARP inhibitors alone (RR 6.80, CI 2.87-16.06 and RR 10.04, CI 2.25-44.75) or chemotherapy alone (RR 13.80, CI 3.43-55.57 and RR 6.57, CI 2.84-15.24). Conclusions: The combination of PARP inhibitors and AAAs did not demonstrate a statistically significant benefit in PFS compared to PARP inhibitors or chemotherapy alone in recurrent ovarian cancer. While the combination therapy was generally well tolerated, hypertension and diarrhea occurred significantly. These findings suggest that combination therapy may not provide a clear survival advantage in the recurrent setting. Further high-quality, biomarker-driven clinical trials are needed to refine patient selection, optimize toxicity management, and determine the potential role of combination therapy in ovarian cancer treatment.
Insights
Combining PARP inhibitors with anti-angiogenic agents (AAAs) did not improve progression-free survival in ovarian cancer patients. This combination therapy led to significantly higher rates of hypertension and diarrhea compared to standard treatments.
Area of Science:
- Gynecologic Oncology
- Medical Oncology
- Clinical Pharmacology
Background:
- Ovarian cancer remains a leading cause of cancer mortality in women.
- Innovative treatment strategies are crucial for improving patient outcomes.
- Combining targeted therapies like PARP inhibitors with anti-angiogenic agents (AAAs) is being explored.
Purpose of the Study:
- To systematically review and meta-analyze the efficacy and safety of combining PARP inhibitors with AAAs for ovarian cancer treatment.
- To compare this combination therapy against PARP inhibitors alone and chemotherapy.
- To assess outcomes based on BRCA mutation status.
Main Methods:
- Systematic literature search of MEDLINE, EMBASE, and Cochrane Library following PRISMA guidelines.
- Inclusion of seven randomized controlled trials (RCTs) involving 2397 patients.
- Meta-analysis of progression-free survival (PFS) and adverse events, with subgroup analyses for BRCA status.
Main Results:
- Combination therapy showed no significant PFS improvement versus PARP inhibitor monotherapy in the general population, BRCA-mutated, or BRCA wild-type subgroups.
- No significant PFS benefit was observed when compared to chemotherapy in recurrent ovarian cancer.
- Hypertension and diarrhea were significantly more frequent with combination therapy.
Conclusions:
- The combination of PARP inhibitors and AAAs does not offer a significant PFS advantage in recurrent ovarian cancer.
- While generally tolerated, the combination therapy increases the risk of hypertension and diarrhea.
- Further research is needed to identify optimal patient selection and toxicity management for this combination.
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