| General information |
| Database: | DB01030 |
| Objective: | neoadjuvant weekly nabpaclitaxel and carboplatin, with bevacizumab and trastuzumab, as treatment for women with locally advanced human epidermal growth factor receptor 2+ breast cancer. |
| Authors: | Denise A. Yardley |
| Title: | Phase II study of neoadjuvant weekly nabpaclitaxel and carboplatin, with bevacizumab and trastuzumab, as treatment for women with locally advanced human epidermal growth factor receptor 2+ breast cancer. |
| Journal: | clinical breast cancer |
| Year: | 2011 |
| PMID: | 21729666 |
| Trial Design |
| Clinical Trial Id: | NCT00392392 |
| Agent: | bevacizumab
|
| Target: | Vascular endothelial growth factor
|
| Cancer Type: | breast cancer |
| Cancer Subtype: | breast cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 13 |
| Therapeutic Combination Content: | neoadjuvant weekly nabpaclitaxel and carboplatin, with bevacizumab and trastuzumab |
| Study Type: | Thisphase II trial examined the feasibility and toxicity of neoadjuvant treatment with bevacizumab added to trastuzumab, nabpaclitaxel, and carboplatin in women with locally advanced human epidermal growth factor receptor II+ breast cancer. |
| Key Patients Feature: | Eligible patients were women with a histologic diagnosis of human epidermal growth factor receptor 2+ invasive adenocarcinoma of the breast with clinical stage T1c4d and/or N03; T1N0M0 cancers were excluded. Tumor human epidermal growth factor receptor 2 assessments required confirmation by fluorescence in situ hybridization (FISH). Additional eligibility criteria included age more than and equal to 18 years, normal left ventricular ejection fraction (LVEF), adequate blood count (white blood cell count more than and equal to 2500/¦ÌL, absolute neutrophil count [ANC]more than and equal to 1500/¦ÌL, hemoglobin countmore than and equal to 9 g/dL, platelet countmore than and equal to 100, 000/¦ÌL), serum creatinine level less than and equal to 1.5 mg/dL ¡Á the institution¡¯s upper limit ofnormal [ULN], and adequate liver function (bilirubin less than and equal to 1.5 ¡Á ULN, transaminase and alkaline phosphatase levels < 2.5 ¡Á ULN). |
| Biomarker: | human epidermal growth factor receptor 2+ |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Twentyeight women with locally advanced human epidermal growth factor receptor 2 breast cancer received nabpaclitaxel (100 mg/m2 intravenously [I.V.] days 1, 8, and 15) and carboplatin (AUC = 6 I.V. day 1) every 28 days ¡Á6 cycles. Concurrent with chemotherapy, trastuzumab (4 mg/kg loading dose, then 2 mg/kg) and bevacizumab (5 mg/kg I.V.) were administered weekly ¡Á 23 weeks. Patients then underwent mastectomy or breastconserving surgery; pathologic responses were assessed. After surgery, trastuzumab 6 mg/kg and bevacizumab 15 mg/kg were administered every 3 weeks (54 weeks total); locoregional radiotherapy and/or antiestrogen therapy was administered per standard guidelines. |
| Primary End Point: | the pCR rate. |
| Secondary End Point: | NA |
| Patients Number: | 28 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | 25 of 26 evaluable patients (96%; 89% of entire group) had objective responses to neoadjuvant chemotherapy (CR, 15; PR, 10). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | The estimated progression free survival at 24 months was 92% (95% CI, 73%98%). |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | In general, neoadjuvant therapy was well tolerated. Grade 3/4 neutropenia was the most common toxicity, occurring in 39% of patients; however there were no episodes of febrile neutropenia. |
| Conclusions: | Neoadjuvant therapy with nabpaclitaxel, carboplatin, trastuzumab, and bevacizumab was feasible in most patients, producing a pCR rate comparable to that in chemotherapytrastuzumab combinations. In contrast, prolonged bevacizumabtrastuzumab therapy after surgical treatment was not well tolerated, primarily due to bevacizumabrelated toxicity. The role of bevacizumab in neoadjuvant therapy remains undefined. |