| General information |
| Database: | DB01035 |
| Objective: | Maintenance capecitabine and bevacizumab versus bevacizumab alone after initial fi rstline bevacizumab and docetaxel for patients with human epidermal growth factor receptor 2negative metastatic breast cancer (IMELDA) |
| Authors: | Joseph Gligorov |
| Title: | Maintenance capecitabine and bevacizumab versus bevacizumab alone after initial firstline bevacizumab and docetaxel for patients with human epidermal growth factor receptor 2negative metastatic breast cancer (IMELDA): a randomised, openlabel, phase 3 trial. |
| Journal: | Lancet Oncology |
| Year: | 2014 |
| PMID: | 25273343 |
| Trial Design |
| Clinical Trial Id: | NCT00929240 |
| 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: | Maintenance capecitabine and bevacizumab |
| Study Type: | a randomised, openlabel, phase III trial |
| Key Patients Feature: | a woman with human epidermal growth factor receptor 2negative metastatic breast cancer with at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST; version 1.0); having an Eastern Cooperative Oncology Group (ECOG) performance status of 1 or 0; a life expectancy of at least 12 weeks; adequate renal, hepatic, and haematological function; being aged 18 years or older; and having not previously received chemotherapy for metastatic breast cancer. Previous adjuvant or neoadjuvant chemotherapy for breast cancer was permitted, provided that the last chemotherapy dose was more than 6 months before starting study treatment. |
| Biomarker: | human epidermal growth factor receptor 2negative |
| Biomark Analysis: | NA |
| Control Group Info: | bevacizumab alone |
| Treatment Info: | each received three to six cycles of fi rstline bevacizumab (15 mg/kg) and docetaxel (75-100 mg/m2) every 3 weeks. progression free patients were randomly assigned with an interactive voiceresponse system by block (size four) randomisation (1:1) to receive either bevacizumab and capecitabine or bevacizumab only (bevacizumab 15 mg/kg on day 1; capecitabine 1000 mg/m2 twice per day on days 1-14, every 3 weeks) until progression, stratified by oestrogen receptor status (positive vs negative), visceral metastases (present vs absent), response status (stable disease vs response vs nonmeasurable), and lactate dehydrogenase concentration (less than and equal to 1.5 vs >1.5 ¡Á upper limit of normal). Neither patients nor investigators were masked to allocation. |
| Primary End Point: | investigatorassessed progression free survival from randomisation, defined as the time from randomisation until disease progression or death. |
| Secondary End Point: | NA |
| Patients Number: | 185 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | 78 (86%) patients in the bevacizumab and capecitabine group and 72 (77%) in the bevacizumab only group had an objective response. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | progression free survival was signifi cantly longer in the bevacizumab and capecitabine group than in the bevacizumab only group (median 11.9 months [95% CI 9.8-15.4] vs 4.3 months [3.9-6.8]; stratifi ed hazard ratio 0.38 [95% CI 0.27-0.55]; twosided logrank p<0.0001) |
| Median OS A vs. C: | median 39.0 months [95% CI 32.3-not reached] vs 23.7 months [18.5-31.7]; stratifi ed HR 0.43 [95% CI 0.26-0.69]; twosided logrank p=0.0003 |
| Adverse Event(agent arm): | Grade 3 or worse adverse events during the maintenancephase were more common with bevacizumab and capecitabine than with bevacizumab only (45 [49%] of 91 patients vs 25 [27%] of 92 patients). The most common grade 3 or worse events were hand-foot syndrome (28 [31%] in the bevacizumab and capecitabine group vs none in the bevacizumab alone group), hypertension (eight [9%] vs three [3%]), and proteinuria (three [3%] vs four [4%]). Serious adverse events were reported by ten (11%) patients in the bevacizumab and capecitabine group and seven (8%) patients in the bevacizumab only group. |
| Conclusions: | Despite prematurely terminated accrual and the lack of information about postprogression treatment, both progression free survival and overall survival they were signifi cantly improved with bevacizumab and capecitabine compared with bevacizumab alone as maintenance treatment. These results might inform future maintenance trials and current fi rstline treatment strategies for human epidermal growth factor receptor 2negative metastatic breast cancer. |