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

Huang,Xuemei; Luo,Jianxiu; Gu,Liqin

doi:10.3892/ol.2024.14782

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

Authors:
- Xuemei Huang
- Jianxiu Luo
- Liqin Gu
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Affiliations: Department of Gynecology, Ganzhou People's Hospital, Ganzhou, Jiangxi 341000, P.R. China
Published online on: October 29, 2024 https://doi.org/10.3892/ol.2024.14782
Article Number: 36
Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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1	Dexter JM, Brubaker LA, Bitler BG, Goff BA, Menon U, Moore KN, Sundaram KM, Walsh CS, Guntupalli SR and Behbakht K: Ovarian cancer think tank: An overview of the current status of ovarian cancer screening and recommendations for future directions. Gynecol Oncol Rep. 53:1013762024. View Article : Google Scholar : PubMed/NCBI
2	Wilson EM, Eskander RN and Binder PS: Recent therapeutic advances in gynecologic oncology: A review. Cancers (Basel). 16:7702024. View Article : Google Scholar : PubMed/NCBI
3	Hirschl N, Leveque W, Granitto J, Sammarco V, Fontillas M and Penson RT: PARP inhibitors: Strategic use and optimal management in ovarian cancer. Cancers (Basel). 16:9322024. View Article : Google Scholar : PubMed/NCBI
4	Goldlust IS, Guidice E and Lee JM: PARP inhibitors in ovarian cancer. Semin Oncol. 51:45–57. 2024. View Article : Google Scholar : PubMed/NCBI
5	Lord CJ and Ashworth A: PARP inhibitors: Synthetic lethality in the clinic. Science. 355:1152–1158. 2017. View Article : Google Scholar : PubMed/NCBI
6	Ferrara N, Hillan KJ, Gerber HP and Novotny W: Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat Rev Drug Discov. 3:391–400. 2004. View Article : Google Scholar : PubMed/NCBI
7	Min T, Lee SH and Lee S: Angiogenesis and apoptosis: Data comparison of similar microenvironments in the corpus luteum and tumors. Animals (Basel). 14:11182024. View Article : Google Scholar : PubMed/NCBI
8	Wei Q and Zhang YH: Flavonoids with anti-angiogenesis function in cancer. Molecules. 29:15702024. View Article : Google Scholar : PubMed/NCBI
9	Ratnaparkhi R, Javellana M, Jewell A and Spoozak L: Evaluation of homologous recombination deficiency in ovarian cancer. Curr Treat Options Oncol. 25:237–260. 2024. View Article : Google Scholar : PubMed/NCBI
10	Collet L, Hanvic B, Turinetto M, Treilleux I, Chopin N, Le Saux I and Ray-Coquard I: BRCA1/2 alterations and reversion mutations in the area of PARP inhibitors in high grade ovarian cancer: State of the art and forthcoming challenges. Front Oncol. 14:13544272024. View Article : Google Scholar : PubMed/NCBI
11	Dellino M, D'Amato A, Battista G, Cormio G, Vimercati A, Loizzi V, Lagana AS, Damiani GR, Favilli A, Gerli S, et al: Reproductive outcomes in women with BRCA 1/2 germline mutations: A retrospective observational study and literature review. Open Med (Wars). 19:202499992024. View Article : Google Scholar : PubMed/NCBI
12	Hockings H and Miller RE: The role of PARP inhibitor combination therapy in ovarian cancer. Ther Adv Med Oncol. 15:175883592311731832023. View Article : Google Scholar : PubMed/NCBI
13	Yi XF, Gao RL, Sun L, Wu ZX, Zhang SL, Huang LT, Han CB and Ma JT: Dual antitumor immunomodulatory effects of PARP inhibitor on the tumor microenvironment: A counterbalance between anti-tumor and pro-tumor. Biomed Pharmacother. 163:1147702023. View Article : Google Scholar : PubMed/NCBI
14	Szentmartoni G, Muhl D, Csanda R, Szasz AM, Herold Z and Dank M: Predictive value and therapeutic significance of somatic BRCA mutation in solid tumors. Biomedicines. 12:5932024. View Article : Google Scholar : PubMed/NCBI
15	Wei Y, He L, Liu T, Guo T, Xie C, Jia J, Lin Y, Liu J and Fan J: Efficacy and safety of PARP inhibitors combined with antiangiogenic agents in the maintenance treatment of ovarian cancer: A systematic review and meta-analysis with trial sequential analysis of randomized controlled trials. Front Pharmacol. 15:13720772024. View Article : Google Scholar : PubMed/NCBI
16	Slim K, Nini E, Forestier D, Kwiatkowski F, Panis Y and Chipponi J: Methodological index for non-randomized studies (minors): Development and validation of a new instrument. ANZ J Surg. 73:712–716. 2003. View Article : Google Scholar : PubMed/NCBI
17	Bernardo WM: PRISMA statement and PROSPERO. Int Braz J Urol. 43:383–384. 2017. View Article : Google Scholar : PubMed/NCBI
18	Guo LL, Cheng TP, Feng LX, Feng J and Li XY: Incidence and risk factors for deep infection after primary shoulder arthroplasty: A meta-analysis. Eur Rev Med Pharmacol Sci. 26:4606–4613. 2022.PubMed/NCBI
19	Lee JM, Moore RG, Ghamande S, Park MS, Diaz JP, Chapman J, Kendrick J, Slomovitz BM, Tewari KS, Lowe ES, et al: Cediranib in combination with olaparib in patients without a germline BRCA1/2 mutation and with recurrent platinum-resistant ovarian cancer: Phase IIb CONCERTO trial. Clin Cancer Res. 28:4186–4193. 2022. View Article : Google Scholar : PubMed/NCBI
20	Lee JY, Kim BG, Kim JW, Lee JB, Park E, Joung JG, Kim S, Choi CH and Kim HS; Korean Gynecologic Oncology Group (KGOG) investigators, : Biomarker-guided targeted therapy in platinum-resistant ovarian cancer (AMBITION; KGOG 3045): A multicentre, open-label, five-arm, uncontrolled, umbrella trial. J Gynecol Oncol. 33:e452022. View Article : Google Scholar : PubMed/NCBI
21	Lheureux S, Oaknin A, Garg S, Bruce JP, Madariaga A, Dhani NC, Bowering V, White J, Accardi S, Tan Q, et al: EVOLVE: A multicenter open-label single-arm clinical and translational phase II trial of cediranib plus olaparib for ovarian cancer after PARP inhibition progression. Clin Cancer Res. 26:4206–4215. 2020. View Article : Google Scholar : PubMed/NCBI
22	Liu JF, Brady MF, Matulonis UA, Miller A, Kohn EC, Swisher EM, Cella D, Tew WP, Cloven NG, Muller CY, et al: Olaparib with or without cediranib versus platinum-based chemotherapy in recurrent platinum-sensitive ovarian cancer (NRG-GY004): A randomized, open-label, phase III trial. J Clin Oncol. 40:2138–2147. 2022. View Article : Google Scholar : PubMed/NCBI
23	Liu G, Feng Y, Li J, Deng T, Yin A, Yan L, Zheng M, Xiong Y, Li J, Huang Y, et al: A novel combination of niraparib and anlotinib in platinum-resistant ovarian cancer: Efficacy and safety results from the phase II, multi-center ANNIE study. EClinicalMedicine. 54:1017672022. View Article : Google Scholar : PubMed/NCBI
24	Liu JF, Barry WT, Birrer M, Lee JM, Buckanovich RJ, Fleming GF, Rimel B, Buss MK, Nattam S, Hurteau J, et al: Combination cediranib and olaparib versus olaparib alone for women with recurrent platinum-sensitive ovarian cancer: A randomised phase 2 study. Lancet Oncol. 15:1207–1214. 2014. View Article : Google Scholar : PubMed/NCBI
25	Mirza MR, Lundqvist EA, Birrer MJ, dePont Christensen R, Nyvang GB, Malander S, Anttila M, Werner TL, Lund B, Lindahl G, et al: Niraparib plus bevacizumab versus niraparib alone for platinum-sensitive recurrent ovarian cancer (NSGO-AVANOVA2/ENGOT-ov24): A randomised, phase 2, superiority trial. Lancet Oncol. 20:1409–1419. 2019. View Article : Google Scholar : PubMed/NCBI
26	Hardesty MM, Krivak TC, Wright GS, Hamilton E, Fleming EL, Belotte J, Keeton EK, Wang P, Gupta D, Clements A, et al: OVARIO phase II trial of combination niraparib plus bevacizumab maintenance therapy in advanced ovarian cancer following first-line platinum-based chemotherapy with bevacizumab. Gynecol Oncol. 166:219–229. 2022. View Article : Google Scholar : PubMed/NCBI
27	Ray-Coquard I, Leary A, Pignata S, Cropet C, González-Martín A, Marth C, Nagao S, Vergote I, Colombo N, Mäenpää J, et al: Olaparib plus bevacizumab first-line maintenance in ovarian cancer: final overall survival results from the PAOLA-1/ENGOT-ov25 trial. Ann Oncol. 34:681–692. 2023. View Article : Google Scholar : PubMed/NCBI
28	Ge Y, Wang Q, Yao Y, Xin Q, Sun J, Chen W, Lin Y and Cai X: Framework nucleic acids-based VEGF signaling activating system for angiogenesis: A dual stimulation strategy. Adv Sci (Weinh). 11:e23087012024. View Article : Google Scholar : PubMed/NCBI
29	Shan Y, Zheng L, Zhang S and Qian B: Abnormal expression of FOXM1 in carcinogenesis of renal cell carcinoma: From experimental findings to clinical applications. Biochem Biophys Res Commun. 692:1492512024. View Article : Google Scholar : PubMed/NCBI
30	Saadi S, Nacer NE, Saari N, Mohammed AS and Anwar F: The underlying mechanism of nuclear and mitochondrial DNA damages in triggering cancer incidences: Insights into proteomic and genomic sciences. J Biotechnol. 383:1–12. 2024. View Article : Google Scholar : PubMed/NCBI
31	Kuroda T and Kohno T: Precision medicine for ovarian clear cell carcinoma based on gene alterations. Int J Clin Oncol. 25:419–424. 2020. View Article : Google Scholar : PubMed/NCBI
32	Boussios S, Rassy E, Moschetta M, Ghose A, Adeleke S, Sanchez E, Sheriff M, Chargari C and Pavlidis N: BRCA mutations in ovarian and prostate cancer: Bench to bedside. Cancers (Basel). 14:38882022. View Article : Google Scholar : PubMed/NCBI
33	Ozols RF: Future directions in the treatment of ovarian cancer. Semin Oncol. 29:32–42. 2002. View Article : Google Scholar : PubMed/NCBI