Multicenter phase II randomized trial evaluating antiangiogenic therapy with sunitinib as consolidation after objective response to taxane chemotherapy in women with HER2-negative metastatic breast cancer
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The aim of this study is to test the hypothesis that antiangiogenic treatment with sunitinib consolidation can prolong remissions induced by taxane-based chemotherapy in women with metastatic breast cancer. The method involves a two-arm open-label (2:1 randomization) multicenter, randomized phase II trial evaluating the efficacy of sunitinib (arm A) versus no therapy (arm B) in patients with HER-2-negative metastatic breast cancer who achieved an objective response to taxane-based chemotherapy. The results of this study indicates that the primary endpoint of progression-free survival (PFS) ≥5 months was achieved in 10 of 36 patients (28%) in arm A and 4 of 19 patients (21%) in arm B. The median PFS was 2.8 and 3.1 months, respectively. A protocol amendment to the sunitinib dosing schedule was made because 53% (17/32) of patients treated at a starting dose of 50 mg (4 weeks on/2 weeks off) required dose reduction. Changing the starting dose to sunitinib 37.5 mg continuously resulted in dose reductions in 44% (7/16) of patients. Grades III–IV toxicity occurred in 69% of patients in arm A (fatigue 31%, musculoskeletal pain 11%, neutropenia and thrombopenia 8%) and 11% in arm B. The proof-of-principle study does not confirm the hypothesis that sunitinib consolidation therapy can lead to a predefined clinically relevant proportion of patients with PFS of ≥5 months after an objective response to taxanes. Furthermore, toxicity was significant.
KeywordsBreast cancer Angiogenesis Sunitinib Consolidation Taxanes
We would like to thank all the participating patients, all the centers who contributed to the study, and Liza Van Eenoo who helped in the coordination of the study and data collection. This study was supported by an unrestricted grant by Pfizer N.V. and used for the performance of this study.
List of recruiting centers and principal investigators: University Hospitals Leuven (Robert Paridaens and Hans Wildiers), Imelda Bonheiden (Wim Wynendaele), AZ St Jan Brugge (Nele Claes), Ziekenhuis Oost Limburg (Jeroen Mebis, Daisy Luyten, Guy Debrock), St-Elisabeth Turnhout (Marc Martens), St-Elisabeth Namen (Peter Vuylsteke and Jean-Charles Goemine), UZ Gent (Hannelore Denys and Veronique Cocquyt), St-Niklaas (Willem Lybaert), Charleroi (Jean-Luc Canon), UZ Brussel (Christel Fontaine and Jacques De Grève), CHC-Liège (Drs C. Focan, MP Graas, F. Kreutz), CHU Sart Tilman Liège (Guy Jerusalem), and Clinique St-pierre Ottignies (Lionel Duck).
Conflict of interest
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