The efficacy and safety of irinotecan ± bevacizumab compared with oxaliplatin ± bevacizumab for metastatic colorectal cancer: A meta-analysis

Abstract

Background: Irinotecan (IRI)-based and oxaliplatin (OXA)-based regimens are available for the treatment of metastatic colorectal cancer (mCRC). Several studies have published inconsistent results in their comparisons of the efficacy and toxicity of IRI ± bevacizumab and OXA ± bevacizumab. This meta-analysis was performed to evaluate the efficacy and safety of these 2 regimens in patients with mCRC.

Methods: We searched several databases to identify relevant studies, including PubMed, EMBASE, and the Cochrane Controlled Trials Register. The primary endpoints were overall survival (OS) and time to progression (TTP). The secondary comparisons were overall response rate (ORR) and toxicity. In addition, the hazard ratio (HR) or risk ratio (RR) values with their corresponding 95% confidence intervals (CIs) were extracted from these studies.

Results: Pooled data of 13 studies demonstrated no significant differences in OS (HR = 0.96, 95% CI: 0.86-1.08, P = .53) and TTP (HR = 0.88, 95% CI: 0.72-1.08, P = .24) between the 2 groups. However, the ORR (RR = 0.87, 95% CI: 0.78-0.97, P = .02) was clearly improved in the OXA ± bevacizumab arm. Higher incidences of grade 3/4 nausea (RR = 1.63, 95% CI: 1.28-2.07, P < .001), vomiting (RR = 1.40, 95% CI: 1.09-1.81, P = .01), diarrhea (RR = 1.44, 95% CI: 1.23-1.70, P < .001), and anemia (RR = 4.13, 95% CI: 2.75-6.22, P < .001) were observed in the IRI group. However, the incidences of grade 3/4 neutropenia (RR = 0.75, 95% CI: 0.68-0.83, P < .001), thrombocytopenia (RR = 0.43, 95% CI: 0.26-0.73, P = .002), and paresthesia/neurological disturbances (RR = 0.04, 95% CI: 0.02-0.07, P < .001) were higher in the OXA group.

Conclusion: This meta-analysis confirmed that the OXA ± bevacizumab regimen as a maintenance therapy significantly improved the ORR in patients with mCRC. Exhibiting strong efficacy and safety, the OXA and OXA plus bevacizumab regimens are preferred as first-line treatments for mCRC.

Figure 1

Flow diagram summarizing the search strategy. Thirteen randomized controlled trials (RCTs) were included the meta-analysis. No differences were found in the baseline characteristics between patients in the 2 groups in the selected studies.

Figure 2

Random-effects model of HR (95% CI) of overall survival associated with the irinotecan group compared with the oxaliplatin group. There are no striking heterogeneity in overall survival was found (P = .005, I² = 59.0%) in the studies. A random-effects model was applied to the meta-analysis. No significant differences were observed in the overall survival between the 2 arms (P = .53). CI = confidence interval, df = degrees of freedom, HR = hazard ratio.

Figure 3

Random-effects model of HR (95% CI) of time to progression associated with the irinotecan group compared with the oxaliplatin group. No striking heterogeneity was found in the time to progression (P < .001, I² = 82.2%) in studies. A random-effects model was applied to the meta-analysis. No significant differences were observed in TTP between the 2 groups (P = .24). CI = confidence interval, df = degrees of freedom, HR = hazard ratio, TTP = time to progression.

Figure 4

RR (95% CI) of overall response rate associated with the irinotecan group compared with the oxaliplatin group. No striking heterogeneity in overall response rate was found (P = .005, I² = 58.0%) in the studies. A random-effects model was applied to the meta-analysis. The overall response rate was inferior in patients who received irinotecan ± bevacizumab compared with those who received oxaliplatin ± bevacizumab (P = .02). CI = confidence interval, df = degrees of freedom, RR = risk ratio.

Figure 5

Begg funnel plots of publication bias test: overall survival. There are no striking heterogeneity in overall survival was found (P = .005, I² = 59.0%) in the studies. The shapes of the funnel plots suggested that the included studies did not have any publication bias. HR = hazard ratio, se = standard error.