Maintenance Therapy in Ovarian Cancer with Targeted Agents Improves PFS and OS: A Systematic Review and Meta-Analysis

Abstract

Background: Maintenance therapy with targeted agents for prolonging remission for ovarian cancer patients remains controversial. As a result, a meta-analysis was conducted to assess the effectiveness and safety of using maintenance therapy with targeted agents for the treatment of ovarian cancer.

Methods: From inception to January 2015, we searched for randomized, controlled trials (RCTs) using the following databases: PubMed, ScienceDirect, the Cochrane Library, Clinicaltrials.gov and EBSCO. Eligible trials included RCTs that evaluated standard chemotherapy which was either followed or not followed by targeted maintenance in patients with ovarian cancer who had been previously receiving adjunctive treatments, such as cytoreductive surgery and standard chemotherapy. The outcome measures included progression-free survival (PFS), overall survival (OS) and incidence of adverse events.

Results: A total of 13 RCTs, which were published between 2006 and 2014, were found to be in accordance with our inclusion criteria. The primary meta-analysis indicated that both PFS and OS were statistically and significantly improved in the targeted maintenance therapy group as compared to the control group (PFS: HR = 0.84, 95%CI: 0.75 to 0.95, p = 0.001; OS: HR = 0.91, 95%CI: 0.84 to 0.98, p = 0.02). When taking safety into consideration, the use of targeted agents was significantly correlated with increased risks of fatigue, diarrhea, nausea, vomiting, and hypertension. However, no significant differences were found in incidence rates of abdominal pain, constipation or joint pain.

Conclusions: Our results indicate that targeted maintenance therapy clearly improves the survival of ovarian cancer patients but may also increase the incidence of adverse events. Additional randomized, double-blind, placebo-controlled, multicenter investigations will be required on a larger cohort of patients to verify our findings.

Fig 1. Flow diagram of trial selection.

Fig 2. Graph of risk bias.

Review of authors' judgments about each factor that was at risk of bias, which are presented as percentages across all included trials.

Fig 3. Hazard ratios of progression-free survival.

SE = standard error; IV = inverse variance method; CI = confidence interval.

Fig 4. Hazard ratios of overall survival.

SE = standard error; IV = inverse variance method; CI = confidence interval.

Fig 5. Risk of discontinuing treatment due to adverse events (CTCAE≥3) in the targeted maintenance therapy group versus the control group.

M-H = Mantel-Haenszel method; CI = confidence interval. CTCAE: Common Terminology Criteria for Adverse Events.