Efficacy and safety of oncolytic viruses in advanced or metastatic cancer: a network meta-analysis

Abstract

Background Oncolytic viruses (OVs) have shown prospects in advanced and metastatic cancer, and many clinical trials have been carried out. To compare OV therapies comprehensively and provide a categorized profile and ranking of efficacy and safety, a network meta-analysis was conducted. Methods A total of 5948 studies were screened and 13 randomized controlled trials with 1939 patients, of whom 1106 patients received OV therapies, comparing four OVs (NTX-010, pexastimogene devacirepvec (Pexa-Vec), talimogene laherparepvec (T-VEC), and pelareorep) were included in a Bayesian network meta-analysis. Eligible studies reported at least one of the following clinical outcome measures: objective response rate (ORR) and grade ≥ 3 adverse events. Results Compared to systemic treatments alone, talimogene laherparepvec (T-VEC) (OR 7.00, 95% CI 1.90–26.00) and T-VEC plus systemic treatment (2.90, 0.80–11.00) showed better objective response rates (ORRs), whereas Pexa-Vec 1 * 109 pfu plus systemic treatment (0.91, 0.26–3.00) and pelareorep plus systemic treatment (1.10, 0.61–2.00) were found to be comparable. The grade ≥ 3 adverse event ranking of the treatments from worst to best was as follows: T-VEC (ranking probability 24%), Pexa-Vec 1 * 109 pfu plus systemic treatment (21%), Pexa-Vec 1 * 109 pfu (17%), T-VEC plus systemic treatment (13%), pelareorep plus systemic treatment (13%), systemic treatments (18%), Pexa-Vec 1 * 108 pfu (12%), and NTX-010 (20%). Conclusions Compared with other oncolytic virus therapies for patients with advanced or metastatic cancer, T-VEC and T-VEC plus systemic treatment appear to provide the best ORR therapy in terms of monotherapy and combination respectively, but should be given with caution to grade ≥ 3 adverse events. Conversely, combining OVs with chemotherapy or target agents was demonstrated not to improve efficacy compared with chemotherapy or target agents alone. Combining OV therapies with immune-checkpoint inhibitors, instead of chemotherapy or target agents, tended to provide better ORRs without causing severe adverse events. This study will guide treatment choice and optimize future trial designs for investigations of advanced or metastatic cancer.

Efficacy and safety of oncolytic virus combined with chemotherapy or immune checkpoint inhibitors in solid tumor patients: A meta-analysis

“…In addition, we performed a subgroup analysis according to hematological and non-hematological toxicity. Previous meta-analyses ( Li Y et al, 2020 ; Li Z et al, 2020 ; Zou et al, 2020 ; Xie et al, 2021 ) have only investigated a series of pairwise comparisons, so they failed to make comparisons without eligible clinical trials. In this study, we included not only RCTs but also selected single-arm trials and therefore gathered together comprehensive data.…”

Oncolytic Virus Engineering and Utilizations: Cancer Immunotherapy Perspective

“…In the past five years, from phase I clinical trials, clinical data have been published with knowledge limiting safety. The general perception is that the OVs are generally safe; in all of those safety studies, adverse effects were limited to grade ≤3 and were observed for OVs with higher objective response rates (ORRs) [173,174]. As of 2 June 2023, 106 studies had undertaken OV in various trial phases, of which 33 studies were completed, according to ClinicalTrials.gov.…”

Insights into immuno-oncology drug development landscape with focus on bone metastasis

“…The results were negative, and patients receiving pelareorep, docetaxel and prednisone vs patients receiving docetaxel and prednisone had no effect on survival. A recent meta-analysis in advanced or metastatic cancer patients indicated that other oncolytic virotherapies may be more effective than pelareorep ( 69 ).…”