Entry Detail
| General information | |
| Database: | DB01040 |
| Objective: | Sorafenib or Placebo with Either Gemcitabine or Capecitabine in Patients with HER2-Negative Advanced Breast Cancer That Progressed during or after Bevacizumab |
| Authors: | Lee S. Schwartzberg |
| Title: | Sorafenib or placebo with either gemcitabine or capecitabine in patients with HER2negative advanced breast cancer that progressed during or after bevacizumab. |
| Journal: | Clinical Cancer Research |
| Year: | 2013 |
| PMID: | 23444220 |
| Trial Design | |
| Clinical Trial Id: | NCT00493636 |
| Agent: | sorafenib |
| Target: | Vascular endothelial growth factor receptor 1 BRaf protooncogene serine/threonineprotein kinase Protooncogene tyrosineprotein kinase receptor ret |
| Cancer Type: | breast cancer |
| Cancer Subtype: | breast cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Sorafenib with either gemcitabine or capecitabine |
| Study Type: | a doubleblind, randomized, placebocontrolledphase IIb screening trial conducted at 40 centers in the United States. |
| Key Patients Feature: | 18 years or older with histologically or cytologically confirmed human epidermal growth factor receptor 2negative adenocarcinoma of the breast with locally advanced (inoperable) or metastatic disease. Patients experienced disease progression during or after a bevacizumab regimen in the adjuvant or metastatic setting. Prior chemotherapy for advanced disease was limited to 1 regimen; prior hormone therapy and radiation therapy were allowed. Additional selection criteria included Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and adequate bone marrow, liver, and renal function. |
| Biomarker: | HER2negative |
| Biomark Analysis: | NA |
| Control Group Info: | placebo plus GEM/CAP |
| Treatment Info: | chemotherapy with sorafenib (400 mg, twice daily) or matching placebo. Initially, chemotherapy was gemcitabine (1, 000 mg/m2 i.v., days 1, 8/21), but later, capecitabine (1, 000 mg/m2 orally twice daily, days 1-14/21) was allowed as an alternative. |
| Primary End Point: | progression free survival (PFS). |
| Secondary End Point: | NA |
| Patients Number: | 160 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | overall response rate was 19.8% versus 12.7%; P = 0.23 |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 3.4 vs. 2.7 months; HR 0.65; 95%confidence interval (CI): 0.45-0.95; P=0.02 |
| Median OS A vs. C: | Median survival was 13.4 versus 11.4 months for sorafenib versus placebo (HR = 1.01; 95% CI: 0.71 1.44; P = 0.95) |
| Adverse Event(agent arm): | sorafenib versus placebo increased grade 3/4 hand-foot skin reaction (39% vs. 5%), stomatitis (10% vs. 0%), fatigue (18% vs. 9%), and dose reductions that were more frequent (51.9% vs. 7.8%). |
| Conclusions: | The addition of sorafenib to gemcitabinecapecitabine provided a clinically small but statistically significant PFS benefit in human epidermal growth factor receptor 2negative advanced breast cancer patients whose disease progressed duringafter bevacizumab. Combination treatment was associated with manageable toxicities but frequently required dose reductions. |