Abstract
BackgroundOncolytic 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.MethodsA 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.ResultsCompared 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%).ConclusionsCompared 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.
Highlights
Oncolytic virus (OV), a new therapeutic approach to cancer treatment, is capable of replicating preferentially within tumour cells and inducing immunogenic cell death [1]
Full list of author information is available at the end of the article
Three OVs in total have been approved for patients with advanced cancers: Rigvir, an RNA virus for melanoma treatment [4]; H101, an adenovirus for the treatment of nasopharyngeal carcinoma [5]; and talimogene laherparepvec (T-VEC), a herpes simplex virus for the treatment of unresectable recurrent melanoma [6]
Summary
Oncolytic virus (OV), a new therapeutic approach to cancer treatment, is capable of replicating preferentially within tumour cells and inducing immunogenic cell death [1]. Current comprehensive treatments for cancers include surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, and so on. Combination therapies have been demonstrated to improve efficacy and cancer management [3]. The species of OVs enrolled in ongoing or completed clinical trials include adenovirus, coxsackievirus, herpes simplex virus, Maraba virus, reovirus, measles virus, vesicular stomatitis virus, Newcastle disease virus, and Seneca Valley virus [7]. A variety of malignancies in different systems have been targeted in OV clinical trials, including melanoma, gastrointestinal cancers, lung cancers, head and neck cancers, genitourinary cancers, breast and gynaecological cancers, and sarcomas [7]. 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
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