Efficacy and safety of olaparib in the treatment of platinum-sensitive recurrent ovarian cancer: a systematic review and meta-analysis
1Department of Obstetrics and Gynecology, Ningbo Women and Children's Hospital, 315012 Ningbo, Zhejiang, China
DOI: 10.22514/ejgo.2022.010 Vol.43,Issue 3,June 2022 pp.46-52
Submitted: 18 March 2022 Accepted: 10 May 2022
Published: 15 June 2022
Background: Olaparib, an orally active inhibitor, has undergone comprehensive clinical evaluation as either single or combination therapy in several solid tumors. To explore the efficacy and safety of Olaparib versus placebo in the treatment of platinum-sensitive recurrent ovarian cancer, we conducted a systematic review and meta-analysis. Methods: We systemically searched through April 30, 2021 PubMed, Cochrane Library, Embase and Web of Science for randomized control trials (RCTs) that compared Olaparib and placebo therapies for platinum-sensitive recurrent ovarian cancer. The primary outcomes were progression-free survival (PFS) and overall survival (OS) evaluated by Hazard ratio (HR) with 95% CI and the secondary outcome was adverse events calculated by the risk ratio (RR) with 95% CI. Results: A total of 3 RCTs, involving 592 patients in the Olaparib group and 359 patients in the placebo therapy, were included. The analysis results of RCTs showed that Olaparib had a significantly better PFS than placebo (HR 0.31; 95% CI 0.26–0.37; p ≤ 0.001), and the pooled OS of the Olaparib group was significantly higher than that of the placebo group (RR 0.73; 95% CI 0.60–0.90; p = 0.003). Regarding safety, the main adverse events included nausea, fatigue, vomiting, anemia, diarrhea, abdominal pain, constipation, headache, dysgeusia and decreased appetite. Conclusions: Olaparib has a positive effect on platinum-sensitive recurrent ovarian cancer as related to progression and overall survival with an increase in adverse events being noted. This meta-analysis demonstrated that Olaparib maintenance therapy is generally well tolerated by the patients.
adverse events; efficacy; meta-analysis; ovarian cancer; olaparib; safety
Yan Wang,Yan Cai,Qiming Wang. Efficacy and safety of olaparib in the treatment of platinum-sensitive recurrent ovarian cancer: a systematic review and meta-analysis. European Journal of Gynaecological Oncology. 2022. 43(3);46-52.
 Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, et al. Cancer statistics in China, 2015. CA: a Cancer Journal for Clinicians. 2016; 66: 115–132.
 Segal R, Miller K, Jemal A. Cancer statistics, 2018. CA: A Cancer Journal for Clinicians. 2018; 68: 7–30.
 Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G, et al. Bevacizumab Combined with Chemotherapy for Platinum-Resistant Recurrent Ovarian Cancer: the AURELIA Open-Label Randomized Phase III Trial. Journal of Clinical Oncology. 2014; 32: 1302–1308.
 Suh DH, Kim M, Lee KH, Eom KY, Kjeldsen MK, Mirza MR, et al. Major clinical research advances in gynecologic cancer in 2017. Journal of Gynecologic Oncology. 2018; 29: e31.
 Gunderson CC, Erickson BK, Buechel ME, Moore KN. The Current Landscape of PARP Inhibitors in Ovarian Cancer. Current Obstetrics and Gynecology Reports. 2018; 7: 20–27.
 Murai J, Huang SN, Das BB, Renaud A, Zhang Y, Doroshow JH, et al. Trapping of PARP1 and PARP2 by Clinical PARP Inhibitors. Cancer Research. 2012; 72: 5588–5599.
 Higgins JPT, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011; 343: d5928–d5928.
 Liang JH, Luo RL. Therapeutic Effects and Safety of Olaparib on Treatment of Recurrent Serosity Ovarian Cancer: a Meta-analysis. CNKI. 2015; 34: 538-542, 547.
 Gao Q, Zhu J, Zhao W, Huang Y, An R, Zheng H, et al. Olaparib Maintenance Monotherapy in Asian Patients with Platinum-Sensitive Relapsed Ovarian Cancer: Phase III Trial (L-MOCA). Clinical Cancer Research. 2022. (in press)
 Ma J, Deng H, Li J, Hu S, Yang Y, Liu S, et al. Efficacy and safety of olaparib maintenance therapy in platinum-sensitive ovarian cancer patients with BRCA mutations: a meta-analysis on randomized controlled trials. Cancer Management and Research. 2019; 11: 3061–3078.
 Guo XX, Wu HL, Shi HY, Su L, Zhang X. The efficacy and safety of olaparib in the treatment of cancers: a meta-analysis of randomized controlled trials. Cancer Management and Research. 2018; 10: 2553–2562.
 Friedlander M, Gebski V, Gibbs E, Davies L, Bloomfield R, Hilpert F, et al. Health-related quality of life and patient-centred out-comes with olaparib maintenance after chemotherapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT Ov-21): a placebo-controlled, phase 3 randomised trial. The Lancet Oncology. 2018; 19: 1126–1134.
 Antoniou A, Pharoah PDP, Narod S, Risch HA, Eyfjord JE, Hopper JL, et al. Average Risks of Breast and Ovarian Cancer Associated with BRCA1 or BRCA2 Mutations Detected in Case Series Unselected for Family History: a Combined Analysis of 22 Studies. The American Journal of Human Genetics. 2003; 72: 1117–1130.
 Bryant HE, Schultz N, Thomas HD, Parker KM, Flower D, Lopez E, et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature. 2005; 434: 913–917.
 Pasanisi P, Bruno E. Breast cancer in BRCA mutations carriers: is it time for a ”lifestyle” primary prevention? Epidemiologia e Prevenzione. 2018; 42: 369–371.
 Cavanagh H, Rogers KMA. The role of BRCA1 and BRCA2 mutations in prostate, pancreatic and stomach cancers. Hereditary Cancer in Clinical Practice. 2015; 13: 16.
 Kuchenbaecker KB, Hopper JL, Barnes DR, Phillips KA, Mooij TM, Roos-Blom MJ, et al. Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers. The Journal of the American Medical Association. 2017; 317: 2402–2416.
 Farmer H, McCabe N, Lord CJ, Tutt ANJ, Johnson DA, Richardson TB, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005; 434: 917–921.
 Deeks ED. Olaparib: first global approval. Drugs. 2015, 75: 231–40.
 Golan T, Hammel P, Reni M, Van Cutsem E, Macarulla T, Hall MJ, et al. Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer. The New England Journal of Medicine. 2019; 381: 317–327.
 Tung NM, Robson ME, Ventz S, Santa-Maria CA, Nanda R, Marcom PK, et al. TBCRC 048: Phase II Study of Olaparib for Metastatic Breast Cancer and Mutations in Homologous Recombination-Related Genes. Journal of Clinical Oncology. 2020; 38: 4274–4282.
 Wang C, Tang H, Geng A, Dai B, Zhang H, Sun X, et al. Rational combination therapy for hepatocellular carcinoma with PARP1 and DNA-PK inhibitors. Proceedings of the National Academy of Sciences. 2020; 117: 26356–26365.
 Hanna C, Kurian KM, Williams K, Watts C, Jackson A, Carruthers R, et al. Pharmacokinetics, safety, and tolerability of olaparib and temozolomide for recurrent glioblastoma: results of the phase I OPARATIC trial. Neuro-Oncology. 2020; 22: 1840–1850.
 Gu Z, Wang L, Yao X, Long Q, Lee K, Li J, et al. ClC-3/SGK1 regulatory axis enhances the olaparib-induced antitumor effect in human stomach adenocarcinoma. Cell Death & Disease. 2020; 11: 898.
 Curt GA, Breitbart W, Cella D, Groopman JE, Horning SJ, Itri LM, et al. Impact of Cancer-Related Fatigue on the Lives of Patients: New Findings from the Fatigue Coalition. The Oncologist. 2000; 5: 353–360.
 Ryan JL, Carroll JK, Ryan EP, Mustian KM, Fiscella K, Morrow GR. Mechanisms of Cancer-Related Fatigue. The Oncologist. 2007; 12: 22–34.
 Bower JE. Cancer-related fatigue—mechanisms, risk factors, and treatments. Nature Reviews Clinical Oncology. 2014; 11: 597–609.
 Zhao H, Sifakis EG, Sumida N, Millán-Ariño L, Scholz BA, Svensson JP, et al. PARP1- and CTCF-Mediated Interactions between Active and Repressed Chromatin at the Lamina Promote Oscillating Transcription. Molecular Cell. 2015; 59: 984–997.
 Klotz DM, Wimberger P. Overcoming PARP inhibitor resistance in ovarian cancer: what are the most promising strategies? Archives of Gynecology and Obstetrics. 2020; 302: 1087–1102.
 Zhou JX, Feng LJ, Zhang X. Risk of severe hematologic toxicities in cancer patients treated with PARP inhibitors: a meta-analysis of randomized controlled trials. Drug Design, Development and Therapy. 2017; 11: 3009–3017.
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