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

Qian X, Qin J, Pan S, Li X, Pan Y, Ma S - PLoS ONE (2015)

Bottom Line: A total of 13 RCTs, which were published between 2006 and 2014, were found to be in accordance with our inclusion criteria.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemotherapy, Hangzhou First People's Hospital, Hangzhou Cancer Hospital, Hangzhou, Zhejiang, P.R. China.

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.

No MeSH data available.


Related in: MedlinePlus

Flow diagram of trial selection.
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pone.0139026.g001: Flow diagram of trial selection.

Mentions: We identified 183 papers from the above discussed databases, and 14 [8, 9, 12–15, 18–25] of these articles were included based on the search criteria, among which 1 trial [23] was excluded because the treatment group undergoing targeted maintenance therapy included only 4 patients. A final total of 13 RCTs were included in our meta-analysis. Our search strategy and the steps used to select eligible trials are summarized in the flow diagram shown in Fig 1 (for detailed information, please see S2 File). Nearly all of the patients in the included trials were initially treated with first-line chemotherapy for 6 cycles. The exceptions included the GOG-0218 trial that evaluated the use of bevacizumab in combination with standard chemotherapy as a first-line treatment in the experimental group [9] and a trial conducted by Meier in which lonafarnib was used for both first-line and maintenance therapy in the experimental group [22]. We included these two trials because of their high quality and clinical significance and also to reduce heterogeneity as much as possible. Among the included trials, 6 were phase III RCTs, and 7 were phase II RCTs. When classifying the included trials based on the mechanisms of targeted agents, 3 used monoclonal antibody, and 10 used small molecule drugs. The characteristics of the 13 included trials are summarized in Table 1.


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

Qian X, Qin J, Pan S, Li X, Pan Y, Ma S - PLoS ONE (2015)

Flow diagram of trial selection.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4581706&req=5

pone.0139026.g001: Flow diagram of trial selection.
Mentions: We identified 183 papers from the above discussed databases, and 14 [8, 9, 12–15, 18–25] of these articles were included based on the search criteria, among which 1 trial [23] was excluded because the treatment group undergoing targeted maintenance therapy included only 4 patients. A final total of 13 RCTs were included in our meta-analysis. Our search strategy and the steps used to select eligible trials are summarized in the flow diagram shown in Fig 1 (for detailed information, please see S2 File). Nearly all of the patients in the included trials were initially treated with first-line chemotherapy for 6 cycles. The exceptions included the GOG-0218 trial that evaluated the use of bevacizumab in combination with standard chemotherapy as a first-line treatment in the experimental group [9] and a trial conducted by Meier in which lonafarnib was used for both first-line and maintenance therapy in the experimental group [22]. We included these two trials because of their high quality and clinical significance and also to reduce heterogeneity as much as possible. Among the included trials, 6 were phase III RCTs, and 7 were phase II RCTs. When classifying the included trials based on the mechanisms of targeted agents, 3 used monoclonal antibody, and 10 used small molecule drugs. The characteristics of the 13 included trials are summarized in Table 1.

Bottom Line: A total of 13 RCTs, which were published between 2006 and 2014, were found to be in accordance with our inclusion criteria.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemotherapy, Hangzhou First People's Hospital, Hangzhou Cancer Hospital, Hangzhou, Zhejiang, P.R. China.

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.

No MeSH data available.


Related in: MedlinePlus