Efficacy and safety of olaparib maintenance therapy in platinum-sensitive ovarian cancer patients with BRCA mutations: a meta-analysis on randomized controlled trials

摘要

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.