Phase II Trial of Sorafenib in Patients With Metastatic Breast Cancer Previously Exposed to Anthracyclines or Taxanes: North Central Cancer Treatment Group and Mayo Clinic Trial N0336

Abstract

PurposeWe conducted a cooperative group phase II study to assess antitumor activity and toxicity of sorafenib in patients with metastatic breast cancer (MBC) who had received prior treatment for their disease.Patient and MethodsPatients were eligible if they had measurable disease and had previously received an anthracycline and/or a taxane in the neoadjuvant, adjuvant, or metastatic setting. The primary end point of the study was tumor response per Response Evaluation Criteria in Solid Tumors (RECIST). The study was designed in two stages. Sorafenib was administered as 400 mg twice daily on days 1 through 28 of each 4-week cycle.ResultsTwenty-three patients were enrolled with a median age of 54 years (range, 37 to 70 years). Twenty-two (96%) had prior anthracycline treatment and 16 (70%) had prior taxane treatment. Patients received sorafenib for a median of two cycles (range, one to 15 cycles) with a median follow-up of 2.4 years (range, 2.2 to 2.6 years). There were no grade 4 toxicities and few grade 3 toxicities. Among the 20 patients eligible for efficacy analysis, no patients experienced a partial response or complete response per RECIST criteria. Thus, the trial stopped at the end of the first stage per study design. Two patients (10%; 90% CI, 1.8% to 28.3%) achieved stable disease lasting longer than 6 months.ConclusionSorafenib as a single agent, although well tolerated, did not exhibit activity when measured by tumor shrinkage in patients with MBC who had received prior treatment. Further research should focus on combinations with standard therapy and end points more sensitive to effects of targeted agents, such as disease stabilization.

Phase II Trial of Dasatinib in Patients with Metastatic Breast Cancer Using Real-Time Pharmacodynamic Tissue Biomarkers of Src Inhibition to Escalate Dosing

“…The majority of patients experienced disease progression prior to 16 weeks (52%) with toxicity (26%) being the second most common reason for study discontinuation. These results are comparable with those reported in a recent phase II trial of sorafenib, an orally available tyrosine kinase inhibitor which also has multiple targets including VEGF receptors, PDGFR, and c-Kit, which was stopped after the first cohort of 23 patients because of lack of efficacy; patients received treatment for a median of two 28-day cycles, and no patients experienced a partial or complete response to therapy (21). In this study, the correlative science was focused on dasatinib's mechanism as an Src inhibitor, and there were no clinically meaningful changes in the tissue levels of p-FAK, p-pax, and p-Src from baseline biopsy to week 4 biopsy.…”

Dasatinib as a Single Agent in Triple-Negative Breast Cancer: Results of an Open-Label Phase 2 Study

“…For example, in two phase 2 studies of patients with metastatic breast cancer previously exposed to anthracyclines or taxanes treated with sorafenib, no patient had a PR or CR (28), and only 3 of 20 (15%) patients with TNBC treated with sunitinib had a PR (29). These results suggest that better patient selection strategies are required.…”

A Phase II Study of Pazopanib in Patients with Recurrent or Metastatic Invasive Breast Carcinoma: A Trial of the Princess Margaret Hospital Phase II Consortium

“…Pazopanib appears to have single-agent activity, including the CBR and TTP, similar to that of other targeted inhibitors of angiogenesis in advanced pretreated breast cancer, such as sunitinib (6-month CBR, 16%; median TTP, 2.3 months) [28], bevacizumab (5-month CBR, 17%; median TTP, 2.4 months) [29], and sorafenib (6-month CBR, 10%-13%; median TTP, 1.9 months) [30,31]. The PFS rate was also similar in our study, with 22% of patients progression free at 6 months (sunitinib, 15%; bevacizumab at 5 months, 16%; sorafenib, 10%).…”