Background: Olaparib, a potent oral poly (ADP-ribose) polymerase inhibitor, exhibits antitumor activity and prevents the recurrence in advanced ovarian cancer. In this article, we assessed the efficacy and safety of olaparib maintenance therapy on platinum-sensitive ovarian cancer patients with BRCA mutations through a meta-analysis of available randomized controlled trials (RCTs) to provide more evidence for its clinical applications.
Methods: We searched PubMed, Embase, Wanfang, CNKI, Web of Science, Cochrane Library, and VIP databases from 1 August 2018 to identify RCTs and finally included four RCTs (seven articles) with 567 eligible participants beyond the participants, interventions, comparisons, outcomes, and study design regulation. The outcomes of olaparib efficacy including progression-free survival (PFS) and overall survival (OS) were measured by HR and 95% CI, while the quality of life was evaluated by calculating the combination of P-value. Seven common adverse events were tested by risk ratio and 95% CI as the outcomes of olaparib safety. These data were analyzed, and the forest figures were produced using Review Manager 5.3.
Results: Compared with other interventions (ie, placebo or chemotherapy drugs), olaparib significantly prolonged PFS (HR=0.31, 95% CI=0.15–0.62) and slightly improved OS (HR=0.75, 95% CI=0.56–0.99), but did not influence the quality of life (P=0.058) in the patients with platinum-sensitive BRCA-mutated ovarian cancer. Additionally, the toxicity profile of olaparib involved anemia, fatigue, vomiting, diarrhea, and nausea with grade 1–2.
Conclusion: This meta-analysis suggests that olaparib maintenance therapy is effective and well-tolerated for the patients with platinum-sensitive BRCA-mutated ovarian cancer. More updated RCTs and long-term follow-up should be conducted to compare and analyze the efficacy and toxicity of olaparib at different doses in ovarian cancer patients.
Keywords: olaparib, ovarian cancer, efficacy, adverse event, meta-analysis
Ovarian cancer is the seventh most common cancer for women overall worldwide.1 In the UK, there were about 7,400 new cases of ovarian cancer in 2014, and it remains the leading cause of death which accounted for 5% of all cancer deaths.2 In the US, there would be approximately 11.6 new cases per 100,000 women and over 6.7 deaths per 100,000 women from the disease in 2015. And in 2018, there will be estimated 22,240 new cases and 14,070 deaths of ovarian cancer.3 In China, there were 52,100 women diagnosed with ovarian cancer and 14,080 patients died of this cancer in 2015.4 Treatments for ovarian cancer including operative therapy, chemotherapy, and targeted therapy are used in clinical practice.5–8
Olaparib (also called lynparza) is an oral, potent inhibitor of poly (ADP-ribose) polymerase (PARP), and its chemical name is 4-[3-(4-cyclopropanecarbonylpiperazine-1-carbonyl)-4-fluorobenzyl]-2H-phthalazin-1-one.9 Olaparib was developed by AstraZeneca Cooperation (London, OH, USA) and used to treat various advanced tumors, including breast, prostate, pancreatic, and ovarian cancers.10–14 In 2014, the FDA and the EMA approved olaparib treatment in germline BRCA-mutated advanced ovarian cancer that has received three or more prior lines of chemotherapy.14–18 Additionally, several Phase II trials have reported that olaparib maintenance therapy in platinum-sensitive relapsed serous ovarian cancer could diminish the tumor size, prolong progression-free survival (PFS), and improve objective responses rate in patients.14,19,20 Meanwhile, it presented an acceptable and manageable tolerability profile and had no worse impact on health-related quality of life.21,22
However, most of these trials have a limitation of small sample size and may not accurately evaluate the efficacy and safety of olaparib. The present study included all available randomized controlled trials (RCTs) according to the criteria of participants, interventions, comparisons, outcomes, and study design (PICOS), and then conducted a meta-analysis to estimate the efficacy and safety of oral olaparib maintenance therapy vs placebo or other chemotherapy drugs among the adult patients with platinum-sensitive BRCA-mutated ovarian cancer. It is expected to provide some evidence on clinical extensive use of olaparib in advanced ovarian cancer.
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