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 |
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| Authors: | Derek J Jonker Patricia A Tang Hagen Kennecke Stephen A Welch M Christine Cripps Timothy Asmis Haji Chalchal Anna Tomiak Howard Lim Yoo-Joung Ko Eric X Chen Thierry Alcindor John R Goffin Grzegorz J Korpanty Harriet Feilotter Ming S Tsao Ashley Theis Dongsheng Tu Lesley Seymour |
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| Affiliation: | 1. Department of Medicine, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada;2. Departments of Medicine and Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada;3. Department of Medicine, BC Cancer Agency, Vancouver, British Columbia, Canada;4. Department of Medical Oncology, University of Western Ontario, London, Ontario, Canada;5. Division of Oncology, Allan Blair Cancer Centre, Regina, Saskatchewan, Canada;6. Department of Oncology, Queen''s University, Kingston, Ontario, Canada;7. Department of Medicine, Sunnybrook Odette Cancer Centre, Toronto, Ontario, Canada;8. Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada;9. Department of Oncology, McGill University, Montréal, Quebec, Canada;10. Department of Oncology, Juravinski Cancer Centre, McMaster University, Hamilton, Ontario, Canada;11. Department of Oncology, Canadian Cancer Trials Group, Queen’s University, Kingston, Ontario, Canada;12. Department of Pathology and Molecular Medicine, Queen''s University, Kingston, Ontario, Canada;13. Department of Laboratory Medicine and Pathobiology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada;14. Department of Oncology, Canadian Cancer Trials Group, Queen’s University, Kingston, Ontario, Canada;15. Department of Mathematics and Statistics, Queen''s University, Kingston, Ontario, Canada |
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| Abstract: | BackgroundOncolytic reovirus pelareorep might preferentially infect and destroy rat sarcoma (RAS)-activated cells, and has preclinical and early clinical activity against colorectal cancer (CRC).Patients and MethodsAfter a 6-patient safety run-in, 103 patients with metastatic CRC were randomly assigned to standard first-line leucovorin/5-FU/oxaliplatin (FOLFOX6)/bevacizumab (FOLFOX/BEV) every 2 weeks with (n = 51) or without (n = 52) pelareorep 3 × 1010 tissue culture infective dose 50 on days 1 to 5 (cycles 1, 2, 4, and alternate cycles thereafter). The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), quality of life, and correlative analyses.ResultsAt 13 months' median follow-up, PFS was inferior in the pelareorep arm (median 7 vs. 9 months; hazard ratio HR], 1.59 80% confidence interval (CI), 1.18-2.15]; P = .046). There was no statistical difference in OS (median, 19.2 vs. 20.1 months; HR, 1.22; P = .38). An increased ORR was observed with pelareorep (adjusted odds ratio, 2.52 80% CI, 1.44-4.41]; P = .03), but with a shorter median duration of response (5 vs. 9 months; P = .028). Pelareorep patients experienced more hypertension and proteinuria, and were more likely to omit bevacizumab before progression. A trend to lower dose intensity and shorter oxaliplatin and bevacizumab treatment duration was observed with pelareorep.ConclusionCombination pelareorep with FOLFOX/BEV was tolerable with an increased ORR, but PFS was inferior. Subgroup analysis of baseline variables including Kirsten rat sarcoma oncogene did not identify subgroups with PFS benefit. Decreased treatment intensity with standard agents likely contributed to the lack of benefit with pelareorep. Future studies might consider alternate pelareorep/chemotherapy strategies or combination therapy with novel agents. |
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| Keywords: | Chemotherapy Oncolytic virus RAS Reolysin Reovirus |
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