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

Abstract

Background: In recent years, several clinical trials have focused on oncolytic virus (OVs) combined with chemotherapy or immune checkpoint inhibitors (ICIs) in solid tumor patients, which showed encouraging effects. However, few studies have concentrated on the summary on the safety and efficacy of the combined treatments. Therefore, we conducted this meta-analysis to explore the safety and curative effect of the combined therapy.Methods: We searched the PubMed, Cochrane Library, Embase, and Clinicaltrials.gov databases to comprehensively select articles on OVs combined with chemotherapy or ICIs for the solid tumor treatment. Overall survival (OS), progression-free survival (PFS), 1-year survival rate, 2-year survival rate, objective response rate (ORR), and adverse events (AEs) were the outcomes.Results: Fifteen studies with 903 patients were included in this meta-analysis. The pooled ORR was 32% [95% confidence interval (CI): 27–36%, I2 = 24.9%, p = 0.239]. Median OS and median PFS were 6.79 months (CI: 4.29–9.30, I2 = 62.9%, p = 0.044) and 3.40 months (CI: 2.59–4.22, I2 = 0.0%, p = 0.715), respectively. The 1-year survival rate was 38% (CI: 0.29–0.47, I2 = 62.9%, p = 0.044), and the 2-year survival rate was 24% (CI: 12–37%, I2 = 0.0%, p = 0.805). The most common AEs were fever (63%, CI: 57–69%, I2 = 2.3%, p = 0.402), fatigue (58%, CI: 51–65%, I2 = 49.2%, p = 0.096), chill (52%, CI: 43–60%, I2 = 0.0%, p = 0.958), and neutropenia (53%, CI: 47–60%, I2 = 0.0%, p = 0.944).Conclusion: OVs combined with ICIs showed a better efficacy than OVs combined with chemotherapy, which lends support to further clinical trials of OVs combined with ICIs. In addition, OVs combined with pembrolizumab can exert increased safety and efficacy. The toxicity of grades ≥3 should be carefully monitored and observed. However, high-quality, large-scale clinical trials should be completed to further confirm the efficacy and safety of OVs combined with ICIs.Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/login.php], identifier [RD42022348568].

Advances in cell-based delivery of oncolytic viruses as therapy for lung cancer

“… 205 So chemotherapy certainly remains an important partner in combination with OV therapy too, although more clinical data are needed to substantiate this. 206 Another important aspect of combinational ICI with chemotherapy or OV therapies in clinical trials so far is the occurrence of patients undergoing complete tumor regression (so-called "elite responders"). Although these elite responders are often only a small fraction of the total amount of patients in each clinical trial, they are nevertheless very valuable and can offer us a way to get important new insights into how immunotherapeutic responses can be improved.…”

PD-1 inhibitor plus oncolytic vaccinia virus is a safe and effective treatment option for metastatic renal cell carcinoma

“…OVs stimulate anti-tumor immune responses, and ICIs function to remove inhibitory signals on effector immune cells. Therefore, it is possible that hematological toxicities, such as neutropenia, anemia, and thrombocytopenia, may occur with combined therapy [ 26 , 27 ]. Furthermore, innate and adaptive immune responses against the virus itself limits the potential of OVs [ 28 ].…”

Effectiveness and safety of pelareorep plus chemotherapy versus chemotherapy alone for advanced solid tumors: a meta-analysis

“…Several meta-analyses have already confirmed that combining oncolytic viruses with chemotherapy is effective and safe for patients with tumors ( Li Z. et al, 2020 ; Li et al, 2020 Y. ; Liu et al, 2022 ). Nonetheless, there are still debates on whether patients with advanced solid tumors can benefit from the treatment of pelareorep combined with palliative chemotherapy.…”