Efficacy and safety of different angiogenesis inhibitors combined with PARP inhibitors in the treatment of ovarian cancer: A systematic review and meta‑analysis

Abstract

Ovarian cancer is a leading cause of mortality among women with gynecological malignancies, largely due to its asymptomatic nature in early stages and frequent late diagnosis. Targeted therapies, such as angiogenesis inhibitors and poly(ADP-ribose) polymerase inhibitors (PARPi), have emerged as promising treatments by disrupting tumor vasculature and impairing DNA repair mechanisms, particularly in patients with BRCA mutations. The objective of the present study was to comprehensively evaluate the combined use of different angiogenesis inhibitors and PARPi in ovarian cancer treatment by meta-analysis. This included assessing their impact on objective response rate (ORR) and progression-free survival (PFS), understanding the role of BRCA mutation status, and comparing the effects of various angiogenesis inhibitors when used in combination with PARPi. The PubMed, Embase and Cochrane databases were searched from inception to February 2024. Only studies on the combined treatment of ovarian cancer with angiogenesis inhibitors and PARPi were included. Duplicate studies, studies with incomplete data, animal studies, literature reviews and systematic studies were excluded. The results underscored a noteworthy improvement in the ORR and median PFS (mPFS) among patients receiving combination therapy compared with those on monotherapy. Specifically, the pooled ORR for combination therapy was significantly higher than that of monotherapy, indicating a substantial benefit in terms of tumor response. Furthermore, combination therapy was found to significantly prolong PFS, offering patients a longer duration without disease progression. Subgroup analyses of patients treated with angiogenesis inhibitors combined with PARPi provided deeper insights, revealing that patients with BRCA mutations exhibited an ORR of 90% compared with 61% in those without BRCA mutations. Additionally, when different angiogenesis inhibitors were compared, patients treated with anti-VEGF agents combined with PARPi showed a longer mPFS (15.53 months) than those treated with TKIs combined with PARPi (7.49 months). In conclusion, the present study demonstrates that combinations of angiogenesis inhibitors and PARPi show great potential for improving treatment outcomes in ovarian cancer, particularly in patients with BRCA mutations. The observed differences in efficacy between various angiogenesis inhibitors highlight the importance of personalized treatment approaches. Further research is warranted to explore the long-term benefits of these combination strategies and refine them to obtain optimal patient outcomes.