Combining Correlated Outcomes and Surrogate Endpoints in a Network Meta-Analysis of Colorectal Cancer Treatments

Abstract

This study aimed to investigate the efficacy and safety of systemic therapies in the treatment of unresectable advanced or metastatic colorectal cancer. Predicted hazard ratios (HRs) and their 95% credible intervals (CrIs) for overall survival (OS) were calculated from the odds ratio (OR) for the overall response rate and/or HR for progression-free survival using multivariate random effects (MVRE) models. We performed a network meta-analysis (NMA) of 49 articles to compare the efficacy and safety of FOLFOX/FOLFIRI±bevacizumab (Bmab)/cetuximab (Cmab)/panitumumab (Pmab), and FOLFOXIRI/CAPEOX±Bmab. The NMA showed significant OS improvement with FOLFOX, FOLFOX+Cmab, and FOLFIRI+Cmab compared with that of FOLFIRI (HR = 0.84, 95% CrI = 0.73–0.98; HR = 0.76, 95% CrI = 0.62–0.94; HR = 0.80, 95% CrI = 0.66–0.96, respectively), as well as with FOLFOX+Cmab and FOLFIRI+Cmab compared with that of FOLFOXIRI (HR = 0.69, 95% CrI = 0.51–0.94 and HR = 0.73, 95% CrI = 0.54–0.97, respectively). The odds of adverse events grade ≥3 were significantly higher for FOLFOX+Cmab vs. FOLFIRI+Bmab (OR = 2.34, 95% CrI = 1.01–4.66). Higher odds of events were observed for FOLFIRI+Pmab in comparison with FOLFIRI (OR = 2.16, 95% CrI = 1.09–3.84) and FOLFIRI+Bmab (OR = 3.14, 95% CrI = 1.51–5.89). FOLFOX+Cmab and FOLFIRI+Bmab showed high probabilities of being first- and second-line treatments in terms of the efficacy and safety, respectively. The findings of the efficacy and safety comparisons may support the selection of appropriate treatments in clinical practice. PROSPERO registration: CRD42020153640.

Comparative Efficacy and Acceptability of Anti-inflammatory Agents on Major Depressive Disorder: A Network Meta-Analysis

“…We also used the trace plot and density plot to assess convergence. Surface under the cumulative ranking curve (SUCRA) is a representative number of the overall ranking, and a lower SUCRA value denotes a lower probability ( Daly et al, 2019 ; Hoang and Kim, 2020 ). We ranked interventions by calculating the values of SUCRA.…”

Cost-minimization analysis of biweekly dosing of cetuximab and FOLFIRI compared with panitumumab and FOLFOX for first-line treatment of patients with KRAS wild-type metastatic colorectal cancer in the United States

“…Based on the network meta-analysis [11] there were no differences in adverse events observed among patients with mCRC receiving cetuximab-FOLFIRI and panitumumab-FOLFOX as first-line treatment. Furthermore, the ASPECCT trial with the head-to-head comparison of cetuximab and panitumumab concluded that the adverse events of any grade were similar except for infusion reaction, skin toxicity, and hypomagnesaemia [32].…”

“…The results showed that cetuximab and panitumumab had similar efficacy and incidence of adverse events; infusion reactions were a key differentiator [10]. Although there is no head-to-head comparison in the first line setting, a recently published network meta-analysis reported no significant difference in either efficacy A c c e p t e d M a n u s c r i p t (hazard ratio 1.01; 95% confidence interval 0.76-1.32) or safety of first-line cetuximab-FOLFIRI compared with panitumumab-FOLFOX [11]. With comparable efficacy and safety, cost may be an important differentiating factor between these treatments.…”