A Randomized Phase II Study of FOLFOX6/Bevacizumab With or Without Pelareorep in Patients With Metastatic Colorectal Cancer: IND.210, a Canadian Cancer Trials Group Trial

Jonker, Derek J.; Tang, Patricia A.; Kennecke, Hagen F.; Welch, Stephen; Cripps, M. Christine; Asmis, Timothy R.; Chalchal, Haji; Tomiak, Anna; Lim, Howard John; Ko, Yoo‐Joung; Chen, Eric X.; Alcindor, Thierry; Goffin, John R.; Korpanty, Grzegorz; Feilotter, Harriet; Tsao, Ming‐Sound; Theis, Ashley; Tu, Dongsheng; Seymour, Lesley

doi:10.1016/j.clcc.2018.03.001

Cited by 46 publications

(25 citation statements)

References 17 publications

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“…Blinding was not performed because of the moral risk associated with the sham injection. In some RCTs [ 19 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ], non-blinding had no significant effect on the efficacy or safety of oncolytic viruses; hence, they were judged as a low-risk factor.…”

Section: Resultsmentioning

confidence: 99%

“…In this meta-analysis, we included the following viruses: T-VEC (herpes virus) [ 26 , 27 ], pelareorep (reovirus) [ 28 , 29 , 30 , 31 , 32 , 33 ], NTX-010 (seneca valley virus; picornavirus) [ 19 ], Ad5-yCD/ mut TK SR39 rep -ADP (adenovirus) [ 34 ], and pexastimogene devacirepvec (Pexa-Vec; poxvirus) [ 35 ]. We first evaluated the efficacy of oncolytic virus from objective response rate (ORR), overall survival (OS), and progression-free survival (PFS); then we analyzed severe adverse events (grade ≥3) and detailed adverse events (AEs).…”

Section: Introductionmentioning

confidence: 99%

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

Jiang

Zhang

et al. 2020

Cancers

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Jiang

Zhang

et al. 2020

Cancers

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“…Recently, a phase 2 clinical study of FOLFOX5/bevacizumab with and without pelareorep virus in patients with metastatic colorectal cancer reported an improved objective response rate of 53 versus 35%, respectively. However, no statistical difference was observed in the overall survival (median 19.2 vs. 20.1 months), and progression-free survival was lower in the pelareorep arm (median 7 vs. 9 months) [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Multimodality Treatment of a Colorectal Cancer Stage IV Patient with FOLFOX-4, Bevacizumab, Rigvir Oncolytic Virus, and Surgery

Tilgase¹,

Olmane

Nazarovs

et al. 2018

Case Rep Gastroenterol

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Colorectal cancer is one of the most commonly diagnosed cancers worldwide. The treatment consists of surgical resection, systemic chemotherapy, and new biological agents. One more recently emerging treatment option is oncolytic virotherapy. Although the use of the new treatment methods shows improved overall and progression-free survival, in general, even with the new treatments, mortality remains high and combinations of treatments should be sought to treat patients with colorectal cancer. Here we report a stage IV colorectal cancer patient who received multimodality treatment including bevacizumab, FOLFOX-4, surgery, and the oncolytic virus Rigvir. The patient shows complete pathological remission and remains stable 7.7 years after initial diagnosis. The possible benefits of combining Rigvir oncolytic virus and bevacizumab should be investigated since in vitro research suggests that anti-angiogenesis agents improve viral distribution by altering the microenvironment of the tumor.

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“…Approaches combining oncolytic viruses with additional immuno-oncology approaches such as ICIs and cellular immunotherapy are ongoing [34]. Recently, a randomized phase II trial of FOLFOX plus bevacizumab with or without pelareorep, an oncolytic reovirus that replicates in RAS mutated cells, in patients with metastatic CRC noted that the study cohort had a statistically increased ORR but also a statistically reduced PFS and duration of response [35]. These mixed results reveal the hurdles that oncolytic viral therapy must still overcome.…”

Section: Novel Combination Therapiesmentioning

confidence: 99%

The Emerging Role of Checkpoint Inhibition in Microsatellite Stable Colorectal Cancer

Hermel

Sigal

2019

JPM

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Checkpoint inhibitor therapy has introduced a revolution in contemporary anticancer therapy. It has led to dramatic improvements in patient outcomes and has spawned tremendous research into novel immunomodulatory agents and combination therapy that has changed the trajectory of cancer care. However, clinical benefit in patients with colorectal cancer has been generally limited to tumors with loss of mismatch repair function and those with specific germline mutations in the DNA polymerase gene. Unfortunately, tumors with these specific mutator phenotypes are in the minority. Recent pre-clinical and clinical studies have begun to reveal encouraging results suggesting that checkpoint inhibitor therapy can be expanded to an increasing number of colorectal tumors with microsatellite stability and the absence of traditional predictive biomarkers of checkpoint inhibitor response. These studies generally rely on combinations of checkpoint inhibitors with chemotherapy, molecular targeted therapy, radiation therapy, or other novel immunomodulatory agents. This article will review the most current data in microsatellite stable colorectal cancer.

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A Randomized Phase II Study of FOLFOX6/Bevacizumab With or Without Pelareorep in Patients With Metastatic Colorectal Cancer: IND.210, a Canadian Cancer Trials Group Trial

Cited by 46 publications

References 17 publications

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

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

Multimodality Treatment of a Colorectal Cancer Stage IV Patient with FOLFOX-4, Bevacizumab, Rigvir Oncolytic Virus, and Surgery

The Emerging Role of Checkpoint Inhibition in Microsatellite Stable Colorectal Cancer

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