| General information |
| Database: | DB01029 |
| Objective: | Paclitaxel Once Per week Compared With Nanoparticle AlbuminBound NabPaclitaxel Once Per week or Ixabepilone With Bevacizumab As FirstLine Chemotherapy for Locally Recurrent or Metastatic Breast Cancer |
| Authors: | Hope S. Rugo |
| Title: | Randomizedphase III Trial of Paclitaxel Once Per week Compared With Nanoparticle AlbuminBound NabPaclitaxel Once Per week or Ixabepilone With Bevacizumab As FirstLine Chemotherapy for Locally Recurrent or Metastatic Breast Cancer: CALGB 40502/NCCTG N063H (Alliance). |
| Journal: | journal of clinical oncology |
| Year: | 2015 |
| PMID: | 26056183 |
| Trial Design |
| Clinical Trial Id: | NCT00785291 |
| Agent: | bevacizumab
|
| Target: | Vascular endothelial growth factor
|
| Cancer Type: | breast cancer |
| Cancer Subtype: | breast cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Nanoparticle AlbuminBound NabPaclitaxel Once Per week or Ixabepilone With Bevacizumab |
| Study Type: | a threearm randomizedphase III trial comparing paclitaxel once per week to nanoparticle albuminbound nabpaclitaxel once per week and to ixabepilone as firstline chemotherapy with bevacizumab for locally recurrent or metastatic BC. |
| Key Patients Feature: | Eligibility included patients age more than and equal to 18 years with histologically documented stage IV or stage IIIC BC not amenable to local therapy, ECOG performance status of 0 to 1, and life expectancy more than and equal to 12 weeks. No prior chemotherapyfor metastatic disease or prior treatment with bevacizumabwas allowed; patients could have received anynumberofprior hormone therapies. Prior taxane therapy in the adjuvant/neoadjuvant setting was allowed ifmetastatic disease occurredmore than and equal to 12months after the last doseoftaxane. Patients with human epidermal growth factor receptor 2-positive (human epidermal growth factor receptor 2positive) disease were eligible if they had previously received trastuzumab or lapatinib. Major surgerymusthavebeencompletedmore than and equal to 28 days before registration. Patients with a historyofresected brain metastases or brain radiation with stable imaging for 3 months were eligible. Measurable disease and adequate bone marrow, renal, and hepatic function were required. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | bevacizumab with paclitaxel 90 mg/m(2) (arm A), nabpaclitaxel 150 mg/m(2) (arm B), or ixabepilone 16 mg/m(2) (arm C) |
| Treatment Info: | patients were randomly assigned to bevacizumab with paclitaxel 90 mg/m2 (arm A), nabpaclitaxel 150 mg/m2 (arm B), or ixabepilone 16 mg/m2 (arm C), once per week for 3 of 4 weeks. |
| Primary End Point: | PFS. |
| Secondary End Point: | NA |
| Patients Number: | 799 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | the overall response rate was 38% for paclitaxel, 34% for nabpaclitaxel, and 27% for ixabepilone |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | Median PFS for paclitaxel was 11 months, ixabepilone was inferior to paclitaxel (PFS, 7.4 months; hazard ratio, 1.59; 95% CI, 1.31 to 1.93; P< .001), and nabpaclitaxel was not superior to paclitaxel (PFS, 9.3 months; hazard ratio, 1.20; 95% CI, 1.00 to 1.45;P=.054). |
| Median OS A vs. C: | a post hoc test of inferiority was significant for ixabepilone compared with paclitaxel (medianOS, 23.6 to 27.4 months; HR, 1.31; 95% CI, 1.03 to 1.66; P=.027) but did not reach significance for nabpaclitaxel compared with paclitaxel (median OS, 23.5 to 26.5 months; HR, 1.17; 95% CI, 0.92 to 1.47; P= .20). |
| Adverse Event(agent arm): | Hematologic and nonhematologic toxicity, including peripheral neuropathy, was increased with nabpaclitaxel, with more frequent and earlier dose reductions. |
| Conclusions: | In patients with chemotherapynaive advanced BC, ixabepilone once per week was inferior to paclitaxel, and nabpaclitaxel was not superior with a trend toward inferiority. Toxicity was increased in the experimental arms, particularly for nabpaclitaxel. Paclitaxel once per week remains the preferred palliative chemotherapy in this setting. |