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.
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Pelareorep, a serotype 3 reovirus, has demonstrated preclinical and early clinical activity in breast cancer and synergistic cytotoxic activity with microtubule targeting agents. This multicentre, randomized, phase II trial was undertaken to evaluate the efficacy and safety of adding pelareorep to paclitaxel for patients with metastatic breast cancer (mBC).
Following a safety run-in of 7 patients, 74 women with previously treated mBC were randomized either to paclitaxel 80 mg/m2 intravenously on days 1, 8, and 15 every 4 weeks plus pelareorep 3 × 1010 TCID50 intravenously on days 1, 2, 8, 9, 15, and 16 every 4 weeks (Arm A) or to paclitaxel alone (Arm B). Primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate, overall survival (OS), circulating tumour cell counts, safety, and exploratory correlative analyses. All comparisons used a two-sided test at an alpha level of 20%. Survival analyses were adjusted for prior paclitaxel.
Final analysis was performed after a median follow-up of 29.5 months. Pelareorep was well tolerated. Patients in Arm A had more favourable baseline prognostic variables. Median adjusted PFS (Arm A vs B) was 3.78 mo vs 3.38 mo (HR 1.04, 80% CI 0.76–1.43, P = 0.87). There was no difference in response rate between arms (P = 0.87). Median OS (Arm A vs B) was 17.4 mo vs 10.4 mo (HR 0.65, 80% CI 0.46–0.91, P = 0.1).
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.
KeywordsBreast cancer Paclitaxel Oncolytic virus Reovirus Phase 2 Randomized
The authors wish to acknowledge Andrew Arnold for his contribution. The authors would like to thank Meredith Carty and Jean Powers for assistance with the manuscript preparation.
This work was supported by the Canadian Cancer Society Research Institute [grant numbers 021039, 704970] and Oncolytics Biotech Inc.
Compliance with ethical standards
Conflicts of interest
The CCTG (L Seymour) received partial financial support from Oncolytics Biotech to offset the costs of the trial. K Gelmon reports having acted as an advisor to Oncolytics Biotech. All the remaining authors have declared no relevant conflicts of interest.
The experiments in this study comply with the current laws of the country in which they were performed.
Informed consent was obtained from all individual participants included in the study.
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