Clinical Overview of Sorafenib in Breast Cancer

Alvaro Moreno-Aspitia


Future Oncol. 2010;6(5):655-663. 

In This Article

Sorafenib as Single Agent in Advanced Breast Cancer

The North Central Cancer Treatment Group (NCCTG) conducted a multicenter Phase II trial (N0336) of single-agent sorafenib in 23 patients previously exposed to anthracycline and taxanes.[49] The primary end point of the study was tumor response, as assessed by the Response Evaluation Criteria In Solid Tumors (RECIST). The study was designed in two stages, and it was temporarily closed after accrual to the first stage of the trial to ascertain whether there was sufficient activity to open enrollment to the second stage of the trial. The analysis was conducted 6 months after the last eligible patient was enrolled. Patients were eligible if they had fewer than two prior chemotherapy regimens in the metastatic setting. A total of 23 patients were enrolled in the first stage of the trial, but three patients were found to be ineligible for efficacy analysis because they had undergone at least two cycles of chemotherapy for MBC. However, all patients were included in the tolerability and toxicity analysis. Sorafenib was administered as 400 mg twice daily on days 1–28 of each 4-week cycle. The median age of patients was 54 years (range: 37–70 years). A total of 22 (96%) patients had prior anthracycline treatment and 16 (70%) had prior taxane treatment. Patients received sorafenib for a median of two cycles (range: 1–15 cycles) with a median follow-up of 2.4 years (range: 2.2–2.6 years). Among the 20 patients eligible for efficacy analysis, no patients experienced a partial response or complete response per RECIST. Thus, the trial stopped at the end of the first stage in accordance with the study design. Two patients (10%; 90% CI: 1.8–28.3%) achieved stable disease lasting longer than 6 months. Overall, treatment was well tolerated and there were no grade 4 toxicities and few grade 3 toxicities. The authors concluded that sorafenib as a single agent, although well tolerated, did not exhibit significant activity, but further research was encouraged focusing on combinations with standard therapy and using end points more sensitive to the effects of targeted agents, such as disease stabilization or clinical benefit rate (CBR).

The second Phase II multicenter trial of single-agent sorafenib in MBC was conducted in Europe by Bianchi et al..[50] Sorafenib was also administered at 400 mg twice a day continuously. The study was initially planned as a Simon two-stage design similar to the NCCTG study. However, based on subsequent data from the advanced renal cell carcinoma trials that demonstrated sorafenib to lead to stabilization of disease more than tumor shrinkage, the study was conducted as a single-stage design and accrued 56 patients. Of these 56 patients, two were deemed ineligible and the other 54 patients received at least one dose of sorafenib. The primary end point was overall best response and secondary end point was percentage of patients with stable disease for at least 16 weeks. Biomarker analyses (plasma levels of VEGF and soluble EGF receptor [sEGFR] and soluble HER-2 [sHER-2] were also performed. In this trial, no patient achieved a complete response, but one patient achieved a partial response (2%). Stabilization of disease was observed in 20 (38%) patients for at least 8 weeks and in 12 (23%) patients for at least 16 weeks. Median time-to-progression (TTP) was 58 days (95% CI: 52–112 days). Sorafenib had manageable toxicity and the most common drug-related grade 3 AEs were rash/desquamation (6%), hand–foot skin reaction (4%) and fatigue (4%). Baseline VEGF levels and levels of sEGFR during treatment and both baseline and changes in sHER-2 levels correlated significantly with clinical outcomes. The authors reached similar conclusions to those from the previous trial: further investigation of single-agent sorafenib in this patient population was not recommended, but studies investigating combinations of sorafenib with chemotherapeutic agents were indeed warranted.


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