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PICASSO III: A Phase III, Placebo-Controlled Study of Doxorubicin With or Without Palifosfamide in Patients With
Christopher W Ryan1, Ofer Merimsky1, Mark Agulnik1
1Christopher W. Ryan, Oregon Health & Science University, Portland, OR; Ofer Merimsky, Sackler School of Medicine, Tel-Aviv, Israel; Mark Agulnik, Northwestern University, Chicago, IL; Jean-Yves Blay, Centre Léon Bérard, Lyon; Antoine Italiano, Institut Bergonié, Bordeaux, France; Scott M. Schuetze, University of Michigan, Ann Arbor, MI; Brian A. Van Tine, Washington University in St Louis, St Louis, MO; Robin L. Jones and Ian R. Judson, The Royal Marsden Hospital, London, United Kingdom; Anthony D. Elias, University of Colorado-Denver, Aurora, CO; Edwin Choy, Massachusetts General Hospital; Jill Y. Buck and Francois Lebel, ZIOPHARM Oncology, Boston, MA; Thierry Alcindor, McGill University Health Center, Montreal, Quebec, Canada; Vicki L. Keedy, Vanderbilt University Medical Center, Nashville, TN; Damon R. Reed, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; Robert N. Taub, Columbia University Medical Center; Jonathan J. Lewis, Samus Therapeutics and Molecular Ninja Group; Robert G. Maki, Mount Sinai School of Medicine, New York, NY; Xavier Garcia del Muro, Institut Català d'Oncologia L'Hospitalet, Barcelona, Spain; and Patrick Schöffski, University Hospitals Leuven, Leuven, Belgium.
Abstract:
Purpose Palifosfamide is the active metabolite of ifosfamide and does not require prodrug activation, thereby avoiding the generation of toxic metabolites. The PICASSO III trial compared doxorubicin plus palifosfamide with doxorubicin plus placebo in patients who had received no prior systemic therapy for metastatic soft tissue sarcoma. Patients and Methods Patients were randomly assigned 1:1 to receive doxorubicin 75 mg/m2 intravenously day 1 plus palifosfamide 150 mg/m2/d intravenously days 1 to 3 or doxorubicin plus placebo once every 21 days for up to six cycles. The primary end point was progression-free survival (PFS) by independent radiologic review. Results In all, 447 patients were randomly assigned to receive doxorubicin plus palifosfamide (n = 226) or doxorubicin plus placebo (n = 221). Median PFS was 6.0 months for doxorubicin plus palifosfamide and 5.2 months for doxorubicin plus placebo (hazard ratio, 0.86; 95% CI, 0.68 to 1.08; P = .19). Median overall survival was 15.9 months for doxorubicin plus palifosfamide and 16.9 months for doxorubicin plus placebo (hazard ratio, 1.05; 95% CI, 0.79 to 1.39; P = .74). There was a higher incidence of grade 3 to 4 adverse events in the doxorubicin plus palifosfamide arm (63.6% v 50.9%) including a higher rate of febrile neutropenia (21.4% v 12.6%). Conclusion No significant difference in PFS was observed in patients receiving doxorubicin plus palifosfamide compared with those receiving doxorubicin plus placebo. The observed median PFS and overall survival in this large, international study can serve as a benchmark for future studies of doxorubicin in metastatic soft tissue sarcoma.
