Comparative safety and efficacy of oncolytic virotherapy for the treatment of individuals with malignancies: a systematic review, meta-analysis, and Bayesian network meta-analysis
Poyee Lau, Long Liang, Xiang Chen, Jianglin Zhang, Hong Liu
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.