A systematic analysis on the clinical safety and efficacy of onco-virotherapy

Abstract

Several onco-virotherapy candidates have been developed and clinically evaluated for the treatment of cancer, and several are approved for clinical use. In this systematic review we explored the clinical impact of onco-virotherapy compared to other cancer therapies by analyzing factors such as trial design, patient background, therapy design, delivery strategies, and study outcomes. For this purpose, we retrieved clinical studies from three platforms: ClinicalTrials.gov, PubMed, and EMBASE. We found that most studies were performed in patients with advanced and metastatic tumors, using a broad range of genetically engineered vectors and mainly administered intratumorally. Therapeutic safety was the most frequently assessed outcome, while relatively few studies focused on immunological antitumor responses. Moreover, only 59 out of 896 clinical studies were randomized controlled trials reporting comparative data. This systemic review thus reveals the need of more, and better controlled, clinical studies to increase our understanding on the application of onco-virotherapy either as a single treatment or in combination with other cancer immunotherapies.

Keywords: cancer; clinical study; immune response; oncolytic virotherapy; outcomes; systematic review; trial.

Graphical abstract

Figure 1

Screening of studies focusing on clinical safety and efficacy of onco-virotherapy (A) Systematic review process and inclusion of articles and trials based on target criteria, where excluded reports were those that did not focus on the application of onco-virotherapy for cancer patients, or were they reviews, preclinical studies, or commentaries, or articles in which the abstract was not reported in English. (B) Geographical distribution of labs and institutes assessing safety and efficacy of onco-virotherapy.

Figure 2

Scenario of clinical studies assessing onco-virotherapy (A) Trends in clinical studies published as trials and articles assessing the role of different onco-virotherapy. (B) Frequency of studies published as trials and articles according to phase and type of onco-virotherapy studied, with the legend the same as in (A). (C) Patient tumor stage and status that received onco-virotherapy. (D) Onco-virotherapy trial status as per ClinicalTrials.gov. (E) Number of cancer patients recruited per study and treated via onco-virotherapy in different phases. (F) Frequency of therapeutic combination with onco-virotherapy.

Figure 3

Viral modifications to improve safety and efficacy (A) Virus modifications to improve tumor specificity. (B) Introduction of transgenes to improve therapeutic efficiency. Each line represents a single study (trial or article).

Figure 4

Strategic design to improve safety and efficacy (A) Trends in choice of viral vector and delivery site according to tumor type. Each line represents a single study (trial or article). (B) Maximum tolerated dose per virus type in patients. (C) Frequency of injections applied.

Figure 5

Clinical outcomes studied related to efficacy (A) Frequent clinical outcomes studied after onco-virotherapy. (B) Type of immunological outcomes studied. (C) Commonly assessed control groups in comparison to onco-virotherapy. (D) Significant improvement or not in clinical outcomes after onco-virotherapy as compared to respective control groups. OS, overall survival; PFS, progression-free survival; ORR, objective response rate; DCR, disease control rate; DLT, dose limiting toxicity; MTD, maximum tolerated dose.

Figure 6

Disparity of data obtained from clinicaltrials.gov and articles Disparities are reported in terms of (A) patient age, (B) follow-up days, (C) sex, (D) combinatorial strategy with onco-virotherapy, (E) funding, (F) inclusion of control group, (G) number of groups per study, (H) patient tumor stage, (I) immunological outcomes studied, (J) type of immunological outcomes studied, and (K) type of onco-virotherapy studied. Bars in red represent clinical trials and in blue represent articles (retrieved from PubMed and EMBASE).