Comparative safety and efficacy of oncolytic virotherapy for the treatment of individuals with malignancies: a systematic review, meta-analysis, and Bayesian network meta-analysis.

Abstract

Background: Oncolytic virotherapy (OV) is an innovative immunotherapy strategy. A comprehensive understanding of oncolytic viruses is essential for advancing research and clinical practice. This analysis aims to evaluate the clinical outcomes of oncolytic virotherapy in cancer patients.

Methods: We performed single-arm, pairwise, and Bayesian network meta-analyses, incorporating clinical trials identified through PubMed, Medline, Embase, and the Cochrane Library from database inception to April 30, 2025. Primary endpoints included all-grade and grade ≥3 adverse events (AEs), objective response rate (ORR), and disease control rate (DCR). Effect size measures included risk ratios (RRs) or odds ratios (ORs) with 95% confidence intervals (CIs) or credible intervals (CrIs). Subgroup analyses were conducted to assess outcomes, and meta-regression was applied to evaluate the influence of prognostic variables. This study is registered with PROSPERO, number CRD42022306458.

Findings: Of 1976 studies screened, 186 clinical trials with 6979 participants met the inclusion criteria. The most common adverse events associated with oncolytic virotherapy were fatigue (1.98%, 1.71-2.28), pyrexia (2.16%, 1.69-2.69), fever (3.32%, 2.64-4.07), and chills (1.65%, 1.39-1.82), with neutropenia (1.07%, 0.67-1.55) and lymphocytopenia (0.71%, 0.51-0.94) being the predominant severe adverse events. While oncolytic virus monotherapy (OV vs immunotherapy, DCR 2.45, 95% CI 1.60-3.76) and combination regimens (OV plus chemotherapy vs OV, DCR 8.53, 95% CI, 1.97-37.03) enhanced therapeutic efficacy, they presented higher toxicity risks compared to conventional treatments (OV vs immunotherapy, all-grade AE 2.07, 95% CI 1.75-2.44). Notably, combination therapies involving chemotherapy (OV plus chemotherapy vs chemotherapy, all-grade AE 1.10, 95% CI 1.02-1.18) or radiotherapy (OV plus radiotherapy vs radiotherapy, all-grade AE 1.53, 95% CI 1.27-1.84) significantly increase adverse event risks. Conversely, oncolytic virotherapy combined with immunotherapy showed a more favorable safety profile (OV plus immunotherapy vs OV plus chemotherapy, severe AE 0.32, 95% CrI 0.15-0.66) and clinical benefits (OV plus immunotherapy vs OV plus chemotherapy, DCR 0.08, 95% CrI 0.02-0.33). Efficacy varied significantly across treatment strategies (adjusted p = 0.040), virus classifications (adjusted p = 0.0027), administration routes (adjusted p = 0.0080), and patient age groups (adjusted p = 0.00080).

Interpretation: This analysis provides robust evidence on the tolerability and efficacy of oncolytic virotherapy in cancer treatment. Oncolytic virotherapy demonstrates significant potential as both monotherapy and in combination regimens, offering a favorable balance of efficacy and safety. Virotherapy paired with immunotherapy exhibits a more favorable safety profile, particularly in regimens involving Reoviridae- or Poxviridae-based strategies. The therapeutic efficacy of oncolytic virotherapy varies notably by multiple factors.

Funding: None.