Addition of targeted agents to chemotherapy for persistent or recurrent ovarian cancer: a meta-analysis of randomized controlled trials

Publication date: Available online 30 June 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Xiao Li, Yuchan Mao, Qiwen Wu, Yuanyuan Liu, Qianqian Wu, Binghuan Wen
AimThe majority of epithelial ovarian cancer patients who achieve a full remission following first-line chemotherapy would finally develop recurrent disease. However, the optimal management of recurrent ovarian cancer (ROC) remains undefined. The preset meta-analysis aims to evaluate the role of novel targeted agents (TAs) in the treatment of ROC in terms of response, overall survival and toxicities.Materials and methodsEligible studies were identified using Medline, Pubmed, and meeting abstracts. Searches were last updated on April 30, 2018. Eligible randomized controlled studies reported survival, toxicities and/or response data for ROC patients receiving novel TAs were included. Primary outcomes of interest were objective response rate (ORR), overall survival (OS), progression free survival (PFS) and adverse events (AEs).ResultsA total of 6,606 patients from 16 studies were eligible for analysis. The pooled results showed that the addition of novel TAs to chemotherapy significantly improved ORR (RR 1.63, 95%CI: 1.33-2.00, p < 0.001), PFS (0.78, 95%CI: 0.68-0.89, p < 0.001) and OS (HR 0.92, 95%CI: 0.87-0.99, p = 0.016) in ROC patients when compared to controls. Similar results in terms of ORR (RR 2.23, p < 0.001), PFS (HR 0.65, p < 0.001), and OS (HR 0.89, p = 0.015) were observed in platinum-sensitive ROC who received TAs. While the addition of novel TAs to chemotherapy significantly improved ORR (RR 1.84, p = 0.002) in platinum-resistant or refractory ROC, it did not translate into PFS (HR 0.83, p = 0.067) and OS (HR 0.94, p = 0.19) benefits. Sub-group analysis according to specific targeted agents showed that combination angiogenesis inhibitors with chemotherapy significantly improved PFS (HR 0.67, p = 0.018), but not for OS (HR 0.93, p = 0.31). As for toxicities, the use of TAs in ROC significantly increased the risk of developing serious AEs (RR 1.27, 95%CI: 1.08-1.50, p = 0.005) and AEs leading to treatment discontinuation (RR 1.93, 95%CI: 1.31-2.84, p = 0.001), but not for fatal AEs (RR: 1.49, 95% CI: 0.89–2.48, p = 0.13). In addition, correlation analysis indicates that PFS (r=0.86, p < 0.001) and ORR (r=0.85, p < 0.001) was strongly correlated with OS for ROC patients received TAs.ConclusionCombination treatment with novel TAs and chemotherapy significantly improved ORR, PFS and OS in platinum-sensitive ROC with an increased risk of severe adverse events. Conversely, we detect no statistically significant survival benefit in platinum-resistant or refractory ROC received TAs. Further prospective randomized studies are needed to confirm our findings and investigate more efficient agents in platinum-resistant or refractory ROC.