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

Abstract

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) > or =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 > or =5 months after an objective response to taxanes. Furthermore, toxicity was significant.

Incidence and risk of hypertension associated with vascular endothelial growth factor receptor tyrosine kinase inhibitors in cancer patients: a comprehensive network meta-analysis of 72 randomized controlled trials involving 30013 patients

“…The highest occurrence (30.8%; 95% CI, 26.7-35.0%) was seen in a Phase III trial for ovarian cancer [69], whereas the lowest overall incidence was detected in ten trials that reported no sign of high-grade hypertensive events [27, 33, 36, 46, 56, 62, 63, 75, 78, 85]. A random-effects model (c 2 -based Q-statistic test: q = 1065.86; P < 0.001; I 2 = 93.4%) revealed that the total occurrence of all-grade hypertensive occasions in cancer patients treated with VEGFR-TKIs was 4.4% (3.7-5.0%, 95% CI, Supplementary Table 4 and Figure S2).…”

Alterations in Cell Cycle and Induction of Apoptotic Cell Death in Breast Cancer Cells Treated withα-Mangostin Extracted from Mangosteen Pericarp

“…Trastuzumab has been shown to induce tumor regression in such patients. Sunitinib, sorafenib, and bevacizumab are multitargeted tyrosine kinase inhibitors that inhibit tumor neovascularization and are currently in clinical trials [2, 3]. These drugs are associated with serious problems such as adverse effects, drug resistance, and low efficacy of single therapy, particularly against metastatic or recurrent breast cancer.…”

Antiangiogenesis Therapy for Breast Cancer: An Update and Perspectives from Clinical Trials

“…In 2010, a multicenter Phase II trial was conducted to evaluate whether sunitinib consolidation could prolong remission after taxane-based chemotherapy in HER-2 negative metastatic breast cancer (MBC) (29). Only 28% of patients achieved the 5-month PFS endpoint after starting sunitinib and due to higher rates of toxicity (69% of Grade 3/4 toxicity), the study failed to confirm the hypothesis.…”