Abstract
Oncolytic virotherapy is a promising antitumor therapeutic strategy. It is based on the ability of viruses to selectively kill cancer cells and induce host antitumor immune responses. However, the clinical outcomes of oncolytic viruses (OVs) vary widely. Therefore, we performed a meta-analysis to illustrate the efficacy and safety of oncolytic viruses. The Cochrane Library, PubMed, and EMBASE databases were searched for randomized controlled trials (RCTs) published up to 31 January 2020. The data for objective response rate (ORR), overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were independently extracted by two investigators from 11 studies that met the inclusion criteria. In subgroup analyses, the objective response rate benefit was observed in patients treated with oncolytic DNA viruses (odds ratio (OR) = 4.05; 95% confidence interval (CI): 1.96–8.33; p = 0.0002), but not in those treated with oncolytic RNA viruses (OR = 1.00, 95% CI: 0.66–1.52, p = 0.99). Moreover, the intratumoral injection arm yielded a statistically significant improvement (OR = 4.05, 95% CI: 1.96–8.33, p = 0.0002), but no such improvement was observed for the intravenous injection arm (OR = 1.00, 95% CI: 0.66–1.52, p = 0.99). Among the five OVs investigated in RCTs, only talimogene laherparepvec (T-VEC) effectively prolonged the OS of patients (hazard ratio (HR), 0.79; 95% CI: 0.63–0.99; p = 0.04). None of the oncolytic virotherapies improved the PFS (HR = 1.00, 95% CI: 0.85–1.19, p = 0.96). Notably, the pooled rate of severe AEs (grade ≥3) was higher for the oncolytic virotherapy group (39%) compared with the control group (27%) (risk difference (RD), 12%; risk ratio (RR), 1.44; 95% CI: 1.17–1.78; p = 0.0006). This review offers a reference for fundamental research and clinical treatment of oncolytic viruses. Further randomized controlled trials are needed to verify these results.
Highlights
Cancer is a common disease globally that seriously affects human health
We included studies in the meta-analysis if they met the following inclusion criteria: (1) the studies were randomized controlled trials in cancer patients treated with an oncolytic virus; (2) the articles had at least one of the following outcomes: objective response rate (ORR), overall survival (OS), progression-free survival (PFS), or adverse events (AEs); (3) cancer patients in the control group received the control regimen without oncolytic virus
A total of 9269 records were retrieved from PubMed, EMBASE, and Cochrane Library
Summary
Cancer is a common disease globally that seriously affects human health. The USA, for instance, projects to have 1,806,590 and 606,520 new cancer cases and cancer deaths, respectively, in 2020 [1]. traditional treatment methods such as radiotherapy, chemotherapy, and targeted drugs are preferred in cancer treatment, their disadvantages include severe adverse events, development of drug resistance, and cross-resistance [2,3]. Oncolytic viruses generally exert antitumor effects by two mechanisms, namely, the selective killing of tumor cells, and induction of antitumor immunity [6]. Oncolytic viruses utilize signaling pathways such as p53, epidermal growth factor receptor (EGFR)/Ras, and protein kinase R (PKR) to target tumor cells for selective expansion [10,11,12,13]. The key steps employed by OVs to transform “cold tumors” into “hot tumors” and activate antitumor immune responses include targeted replication, the release of tumor-associated antigens through oncolysis, upregulation of chemokines and danger signals, recruitment of dendritic cells and lymphoid cells, and upregulation of immune checkpoint molecules [16,17,18]
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