| General information |
| Database: | DB01039 |
| Objective: | A Study of Avastin (Bevacizumab) in Combination With Herceptin (Trastuzumab)/Docetaxel in Patients With human epidermal growth factor receptor 2 Positive Metastatic Breast Cancer. |
| Authors: | Luca Gianni |
| Title: | AVEREL: a randomizedphase III Trial evaluating bevacizumab in combination with docetaxel and trastuzumab as firstline therapy for human epidermal growth factor receptor 2positive locally recurrent/metastatic breast cancer. |
| Journal: | journal of clinical oncology |
| Year: | 2013 |
| PMID: | 23569311 |
| Trial Design |
| Clinical Trial Id: | NCT00391092 |
| 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: | bevacizumab + docetaxel and trastuzumab |
| Study Type: | AVEREL [A Study of Avastin (Bevacizumab) in Combination With Herceptin (Trastuzumab)/Docetaxel in Patients With human epidermal growth factor receptor IIPositive Metastatic Breast Cancer] was an openlabel, randomized, controlledphase III trial. |
| Key Patients Feature: | human epidermal growth factor receptor 2positive measurable or evaluable locally recurrent or metastatic breast cancer (LR/MBC; centrally confirmed immunohistochemistry3 orfluorescencein situ hybridizationorchromogenicin situ hybridization positive); had received no prior trastuzumab or chemotherapy for LR/MBC; had Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; were age more than and equal to 18 years; had baseline left ventricular ejection fractionmore than and equal to 50% according to echocardiogram or multigated acquisition scan; had adequate bone marrow, liver, and renal function; and had no CNS metastases. Other drugspecific eligibility criteria were similar to those in previousphase III trials oftrastuzumabandbevacizumabinLR/MBC.Patients who had received adjuvant trastuzumab were eligible if relapse was more than and equal to 6 months after the last trastuzumab dose. Previous adjuvant taxane was permitted if receivedmore than and equal to 12 months before random assignment |
| Biomarker: | Blood samples for plasma marker analysis |
| Biomark Analysis: | High baseline plasma vascular endothelial growth factor A (VEGFA) concentrations were associated with greater bevacizumab benefit (not statistically significant). |
| Control Group Info: | nonbevacizumab arm |
| Treatment Info: | docetaxel 100 mg/m2 plus trastuzumab 8 mg/kg loading dose followed by 6 mg/kg either with bevacizumab 15 mg/kg or without bevacizumab, all administered every 3 weeks. |
| Primary End Point: | progression free survival (PFS). |
| Secondary End Point: | overall survival, response rate (RR), safety, quality of life, and translational research. |
| Patients Number: | 424 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | investigatorassessed ORR (69.9% with TH v 74.3% with BTH; P= .3492). Complete responses were observed in 5.7% and 5.5% of patients, respectively. IRCassessed ORRs were 65.9% versus 76.5%, respectively (P= .0265). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | HR=0.82; 95% CI, 0.65 to 1.02; P= .0775; median PFS, 13.7 v 16.5 months in the nonbevacizumab and bevacizumab arms, respectively; PFS events in 72% |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Grade more than and equal to 3 febrile neutropenia and hypertension were more common with bevacizumabcontaining therapy. |
| Conclusions: | Combining bevacizumab with docetaxel and trastuzumab did not significantly improve investigatorassessed PFS. The potential predictive value of plasma VEGFA is consistent with findings in human epidermal growth factor receptor 2negative LRMBC, warranting prospective evaluation. |