| General information |
| Database: | DB00985 |
| Objective: | Randomisedphase 3 trials in metastatic breast cancer have shown that combining bevacizumab with either paclitaxel or capecitabine significantly improves progression free survival and response rate compared with chemotherapy alone but the relative efficacy of bevacizumab plus paclitaxel versus bevacizumab plus capecitabine has not been investigated. they compared the efficacy of the two regimens. |
| Authors: | Lang I, et al |
| Title: | Bevacizumab plus paclitaxel versus bevacizumab plus capecitabine as firstline treatment for human epidermal growth factor receptor 2negative metastatic breast cancer: interim efficacy results of the randomised, openlabel, noninferiority, phase 3 TURANDOT trial. |
| Journal: | Lancet Oncol. |
| Year: | 2013 |
| PMID: | 23312888 |
| Trial Design |
| Clinical Trial Id: | NCT00600340 |
| Agent: | Bevacizumab
|
| Target: | Vascular endothelial growth factor
|
| Cancer Type: | breast cancer |
| Cancer Subtype: | human epidermal growth factor receptor 2positive advanced breast cancer (ABC) |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Bevacizumab + paclitaxel |
| Study Type: | randomised, openlabel, noninferiority, phase III TURANDOT trial |
| Key Patients Feature: | patients with human epidermal growth factor receptor 2negative metastatic breast cancer who had received no chemotherapy for advanced disease |
| Biomarker: | human epidermal growth factor receptor 2negative |
| Biomark Analysis: | as in the conclusion |
| Control Group Info: | Bevacizumab plus paclitaxel versus bevacizumab plus capecitabine |
| Treatment Info: | pts were randomised (by computergenerated sequence; 1:1 ratio; block size six; stratified by hormone receptor status, country, and menopausal status) to receive either intravenous bevacizumab (10 mg/kg on days 1 and 15) plus intravenous paclitaxel (90 mg/m(2) on days 1, 8, and 15) repeated every 4 weeks (paclitaxel group) or intravenous bevacizumab (15 mg/kg on day 1) plus oral capecitabine (1000 mg/m(2) twice daily on days 114) repeated every 3 weeks (capecitabine group) until disease progression or unacceptable toxic effects. |
| Primary End Point: | noninferior overall survival with bevacizumab plus capecitabine versus bevacizumab plus paclitaxel |
| Secondary End Point: | NA |
| Patients Number: | 564 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | bevacizumab plus paclitaxel vs bevacizumab plus capecitabine: 44% vs 27% |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | bevacizumab plus paclitaxel vs bevacizumab plus capecitabine: median progression free survival 11.0 months [95% CI 10.412.9] vs 8.1 months [7.19.2]; HR 1.36 [95% CI 1.091.68], p=0.0052 |
| Median OS A vs. C: | 1year overall survival was 81% (95% CI 77-86%) in the paclitaxel group and 79% (74-84%) in the capecitabine group; 2year overall survival was 60% (52-67%) in the paclitaxel group and 55% (47-63%) in the capecitabine group. |
| Adverse Event(agent arm): | The most common adverse events of grade 3 or higher were neutropenia, peripheral neuropathy, and leucopenia for bevacizumab plus paclitaxel and handfoot syndrome, hypertension, and diarrhoea for bevacizumab plus capecitabine. 15% of patients in both groups had adverse events that led to bevacizumab discontinuation (42 of 284 in the paclitaxel group vs 42 of 277 in the capecitabine group). however, chemotherapy was discontinued because of adverse events more frequently in the paclitaxel group (109 [38%]) than the capecitabine group (53 [19%]). In the paclitaxel group, one patient died from an adverse event deemed by the investigator to be treatment related (haemorrhage). No treatmentrelated deaths occurred in the capecitabine group. |
| Conclusions: | In this planned interim analysis, the noninferiority criterion was not met and overall survival results are inconclusive. Final results are expected in 2014. progression free survival was better, and more patients achieved an objective response, with bevacizumab plus paclitaxel than with bevacizumab plus capecitabine. Efficacy results in both groups they were consistent with previous reports. |