Efficacy and Safety of Oncolytic Viruses in Randomized Controlled Trials: A Systematic Review and Meta-Analysis

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.

Mesenchymal stem cells and oncolytic viruses: joining forces against cancer

“…However, while local OVs administration has shown promising results in melanoma patients, systemic OVs administration has reported only occasional and transient responses. 5 The inadequate delivery of OVs to the tumor, as a result of liver or spleen sequestration, immune system recognition and elimination, and poor tumor extravasation and spread, has been identified as a main factor for insufficient antitumor efficacy after systemic OVs administration. 3 It is, therefore, of clinical relevance to develop new strategies to improve OVs bioavailability and delivery to tumors, especially for those patients where intratumoral injection is not feasible or with tumor metastases.…”

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

“…Compared with the reported meta-analyses of OV therapies, this network meta-analysis had several strengths [ 35 – 37 ]. To date, there has been no network meta-analysis to comprehensively describe the efficacy and safety of optional OV therapies; thus, our study established comparisons among all eligible OV monotherapies and combination therapies.…”

The role of NK cells in oncolytic viral therapy: a focus on hepatocellular carcinoma

“…Participants were either randomised to JX-594 and best supportive care (BSC) or BSC alone. Unfortunately, there was no Anti-tumour activity dependant on cancer cell lines and degree of ZAP deficiency [92] M1 oncolytic virus plus anti-PD-1 antibody and Apatinib…”

“…However, pre-clinical studies showed disappointing efficacy highlighting the potential requirement for combination therapy and additional genetic engineering of the virus to improve efficacy. Inhibitors of valosin-containing protein have been observed to be specific inductors of oncolysis in HCC by promoting stress-induced apoptosis [92] . A phase 1 trial (NCT04665362) has now been approved to determine the safety, tolerability & efficacy of the M1 virus combined with an anti-PD-1 (SHR-1201) antibody and Apatinib, a tyrosine kinase inhibitor in patients with advanced HCC.…”