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

H. Wildiers (1) , C. Fontaine (2) , P. Vuylsteke (3) , M. Martens (4) , J. L. Canon (5) , W. Wynendaele (6) , C. Focan (7) , J. Greve (2) , P. Squifflet (8) , R. Paridaens (1)

1 Department of General Medical Oncology/Multidisciplinary Breast Centre
2 Department of Medical Oncology
3 Department of Oncology
4 Department of Oncology-Radiology
5 Department of Oncology-Hematology and Radiology
6 Department of Oncology-Radiotherapy
7 Department of Oncology-Hemato-Immunology
8 IDDI

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.

Mots clés: Breast cancer; Angiogenesis; Sunitinib; Consolidation; Taxanes

H. Wildiers, C. Fontaine, P. Vuylsteke, M. Martens, J. L. Canon, et al.. 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. Breast Cancer Research and Treatment, 2010, 123 (2), pp.463-469. ⟨10.1007/s10549-010-1066-x⟩. ⟨hal-00558513⟩