Abstract
Several approaches to active immunotherapy for melanoma, including peptide-based vaccines (PVs), autologous tumour cell vaccines (TCVs), allogeneic TCVs and autologous dendritic cell vaccines (DCVs), have been investigated in clinical trials. However, comprehensive evidence comparing these interventions remains unavailable. The objective of this study was to expand previous work to compare and rank the immunotherapeutic strategies for melanoma in terms of overall survival and toxic effects with a Bayesian network meta-analysis. Methodologically, we performed a network meta-analysis of head-to-head randomized controlled trials comparing and ranking cancer vaccine approaches for patients with melanoma. PubMed, MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, the WHO International Clinical Trials Registry Platform and ClinicalTrials.gov were searched up to 31 July 2020. We estimated summary hazard ratios for death and risk ratios for toxicity. The effects of the underlying prognostic variable on survival benefits were examined by meta-regression. We performed subgroup analysis for the outcomes based on metastatic categories. Overall, we identified 4776 citations, of which 15 head-to-head randomized controlled trials (3162 participants) were included in the analysis. In terms of efficacy, allogeneic tumour cell vaccines plus immunotherapy adjuvants, peptide-based vaccines plus immunotherapy adjuvants and standard therapy were more effective than peptide vaccines. The proportion of women was inversely associated with mortality risk. For safety, all treatments were inferior to allogeneic tumour cell vaccines except for allogeneic tumour cell vaccines plus chemotherapy. Peptide vaccines plus immunotherapy adjuvants led to an increased risk of adverse events compared to allogeneic tumour cell vaccines plus immunotherapy adjuvants. These results suggest that allogeneic TCV and autologous DCV are better than standard therapy. PV plus immune modulators are the most effective strategy among all comparable strategies but is associated with increased toxicity. Any combination regimens for cancer therapeutic vaccines need to be balanced between risk and benefit profiles.