A randomized phase II study of weekly paclitaxel with or without pelareorep in patients with metastatic breast cancer: final analysis of Canadian Cancer Trials Group IND.213.

Bernstein, Vanessa; Ellard, Susan L.; Dent, Susan; Tu, Dongsheng; Mates, Mihaela; Dhesy‐Thind, Sukhbinder; Panasci, Lawrence; Gelmon, Karen A.; Salim, Mohammad; Song, Xinni; Clemons, Mark; Ksienski, Doran; Verma, Shailendra; Simmons, Christine; Lui, Hongbo; N., Kim; Feilotter, Harriet; Hagerman, Linda; Seymour, Lesley

doi:10.1007/s10549-017-4538-4

Cited by 76 publications

(59 citation statements)

References 25 publications

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“…The Canadian Cancer Trials Group (CCTG) presented positive OS data from an open-label, randomized, phase II study assessing the therapeutic combination of IV-administered pelareorep given in combination with paclitaxel versus paclitaxel alone, in patients with advanced or metastatic breast cancer [ 33 ]. The 74 patient study, powered to 90% and designed by the CCTG, reported a statistically significant improvement in median OS from 10.4 months on the control arm to 17.4 months on the test arm (hazard ratio 0.65, 80% CI from 0.46 to 0.91, p = 0.1), although no corresponding difference in median PFS was seen between the test arm and control arm (3.8 month versus 3.4 months, hazard ratio 1.04, 80% CI from 0.76 to 1.43, p = 0.87).…”

Section: Discussionmentioning

confidence: 99%

A Phase II Study of Pelareorep (REOLYSIN®) in Combination with Gemcitabine for Patients with Advanced Pancreatic Adenocarcinoma

Mahalingam

Goel

Aparo

et al. 2018

Cancers

101

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Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with 1 and 5-year survival rates of ~18% and 7% respectively. FOLFIRINOX or gemcitabine in combination with nab-paclitaxel are standard treatment options for metastatic disease. However, both regimens are more toxic than gemcitabine alone. Pelareorep (REOLYSIN®), a proprietary isolate of reovirus Type 3 Dearing, has shown antitumor activity in clinical and preclinical models. In addition to direct cytotoxic effects, pelareorep can trigger antitumor immune responses. Due to the high frequency of RAS mutations in PDAC, we hypothesized that pelareorep would promote selective reovirus replication in pancreatic tumors and enhance the anticancer activity of gemcitabine. Chemotherapy-naïve patients with advanced PDAC were eligible for the study. The primary objective was Clinical Benefit Rate (complete response (CR) + partial response (PR) + stable disease (SD) ≥ 12 weeks) and secondary objectives include overall survival (OS), toxicity, and pharmacodynamics (PD) analysis. The study enrolled 34 patients; results included one partial response, 23 stable disease, and 5 progressive disease. The median OS was 10.2 months, with a 1- and 2-year survival rate of 45% and 24%, respectively. The treatment was well tolerated with manageable nonhematological toxicities. PD analysis revealed reovirus replication within pancreatic tumor and associated apoptosis. Upregulation of immune checkpoint marker PD-L1 suggests future consideration of combining oncolytic virus therapy with anti-PD-L1 inhibitors. We conclude that pelareorep complements single agent gemcitabine in PDAC.

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Section: Discussionmentioning

confidence: 99%

A Phase II Study of Pelareorep (REOLYSIN®) in Combination with Gemcitabine for Patients with Advanced Pancreatic Adenocarcinoma

Mahalingam

Goel

Aparo

et al. 2018

Cancers

101

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“…This OV has provided particularly promising evidence, and use in Phase II trials have increased OS in multiple cancers. In one study of 74 patients with metastatic breast cancer, OS increased as compared to paclitaxel monotherapy (17·4 months vs. 10·4 months) [ 114 ]. In a smaller study of 14 patients with melanoma, the addition of Reolysin to paclitaxel and carboplatin saw a 21% ORR (3 patients) [ 111 ].…”

Section: Reolysinmentioning

confidence: 99%

Clinical Application of Oncolytic Viruses: A Systematic Review

Cook

Chauhan

2020

IJMS

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Leveraging the immune system to thwart cancer is not a novel strategy and has been explored via cancer vaccines and use of immunomodulators like interferons. However, it was not until the introduction of immune checkpoint inhibitors that we realized the true potential of immunotherapy in combating cancer. Oncolytic viruses are one such immunotherapeutic tool that is currently being explored in cancer therapeutics. We present the most comprehensive systematic review of all oncolytic viruses in Phase 1, 2, and 3 clinical trials published to date. We performed a systematic review of all published clinical trials indexed in PubMed that utilized oncolytic viruses. Trials were reviewed for type of oncolytic virus used, method of administration, study design, disease type, primary outcome, and relevant adverse effects. A total of 120 trials were found; 86 trials were available for our review. Included were 60 phase I trials, five phase I/II combination trials, 19 phase II trials, and two phase III clinical trials. Oncolytic viruses are feverously being evaluated in oncology with over 30 different types of oncolytic viruses being explored either as a single agent or in combination with other antitumor agents. To date, only one oncolytic virus therapy has received an FDA approval but advances in bioengineering techniques and our understanding of immunomodulation to heighten oncolytic virus replication and improve tumor kill raises optimism for its future drug development.

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“…However, there was no significant difference in the progression-free survival (PFS) as a primary endpoint, and the median overall survival in arm A was significantly longer than arm B (17.4 and 10.4 months, respectively). This trial suggests that the combination of paclitaxel and pelareorep is more effective than paclitaxel alone [ 105 ].…”

Section: Oncolytic Viruses and Breast Cancermentioning

confidence: 99%

The Current Status and Future Prospects of Oncolytic Viruses in Clinical Trials against Melanoma, Glioma, Pancreatic, and Breast Cancers

Eissa

Bustos-Villalobos

Ichinose

et al. 2018

Cancers

134

102

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Oncolytic viral therapy has been accepted as a standard immunotherapy since talimogene laherparepvec (T-VEC, Imlygic®) was approved by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) for melanoma treatment in 2015. Various oncolytic viruses (OVs), such as HF10 (Canerpaturev—C-REV) and CVA21 (CAVATAK), are now actively being developed in phase II as monotherapies, or in combination with immune checkpoint inhibitors against melanoma. Moreover, in glioma, several OVs have clearly demonstrated both safety and a promising efficacy in the phase I clinical trials. Additionally, the safety of several OVs, such as pelareorep (Reolysin®), proved their safety and efficacy in combination with paclitaxel in breast cancer patients, but the outcomes of OVs as monotherapy against breast cancer have not provided a clear therapeutic strategy for OVs. The clinical trials of OVs against pancreatic cancer have not yet demonstrated efficacy as either monotherapy or as part of combination therapy. However, there are several oncolytic viruses that have successfully proved their efficacy in different preclinical models. In this review, we mainly focused on the oncolytic viruses that transitioned into clinical trials against melanoma, glioma, pancreatic, and breast cancers. Hence, we described the current status and future prospects of OVs clinical trials against melanoma, glioma, pancreatic, and breast cancers.

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A randomized phase II study of weekly paclitaxel with or without pelareorep in patients with metastatic breast cancer: final analysis of Canadian Cancer Trials Group IND.213.

Abstract: This first, phase II, randomized study of pelareorep and paclitaxel in previously treated mBC did not show a difference in PFS (the primary endpoint) or RR. However, there was a significantly longer OS for the combination. Further exploration of this regimen in mBC may be of interest.

Cited by 76 publications

References 25 publications

A Phase II Study of Pelareorep (REOLYSIN®) in Combination with Gemcitabine for Patients with Advanced Pancreatic Adenocarcinoma

A Phase II Study of Pelareorep (REOLYSIN®) in Combination with Gemcitabine for Patients with Advanced Pancreatic Adenocarcinoma

Clinical Application of Oncolytic Viruses: A Systematic Review

The Current Status and Future Prospects of Oncolytic Viruses in Clinical Trials against Melanoma, Glioma, Pancreatic, and Breast Cancers

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