Entry Detail
| General information | |
| Database: | DB00012 |
| Objective: | To evaluate the efficacy and safety of bevacizumab when added to firstline oxaliplatinbased chemotherapy (either capecitabine plus oxaliplatin [XELOX] or fluorouracil/folinic acid plus oxaliplatin [FOLFOX4]) in patients with metastatic colorectal cancer (MCRC). |
| Authors: | Saltz LB, et al |
| Title: | Bevacizumab in combination with oxaliplatinbased chemotherapy as firstline therapy in metastatic colorectal cancer: a randomizedphase III study. |
| Journal: | J Clin Oncol. |
| Year: | 2008 |
| PMID: | 18421054 |
| Trial Design | |
| Clinical Trial Id: | NA |
| Agent: | bevacizumab |
| Target: | Vascular endothelial growth factor Epidermal growth factor receptor |
| Cancer Type: | colorectal cancer |
| Cancer Subtype: | advanced colorectal cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | either capecitabine+oxaliplatin [XELOX] or fluorouracil/folinic acid+oxaliplatin [FOLFOX4]+Bevacizumab |
| Study Type: | A Randomizedphase III Study |
| Key Patients Feature: | Patients age more than and equal to 18 years with histologically confirmed MCRC, one or more unidimensionally measurable lesions, who were not felt to be amenable to curative resection |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | XELOX or FOLFOX4+ placebo |
| Treatment Info: | Patients with MCRC were randomly assigned, in a 2 x 2 factorial design, to XELOX versus FOLFOX4, and then to bevacizumab versus placebo. |
| Primary End Point: | PFS noninferiority of XELOX with or without bevacizumab versus FOLFOX4 with or without bevacizumab. |
| Secondary End Point: | effect on PFS of bevacizumab versus placebo when combined with oxaliplatinbased chemotherapy (XELOX or FOLFOX4). |
| Patients Number: | 1401 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | Response rates were similar in both arms;Analysis of treatment withdrawals shotheyd that, despite protocol allowance of treatment continuation until disease progression, only 29% and 47% of bevacizumab and placebo recipients, respectively, were treated until progression |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 9.4 ms vs 8.0 ms ([HR], 0.83; 97.5% CI, 0.72 to 0.95; P =0.0023). |
| Median OS A vs. C: | 21.3 ms vs 19.9 ms (HR, 0.89; 97.5% CI, 0.76 to 1.03; P =0.077). |
| Adverse Event(agent arm): | The toxicity profile of bevacizumab was consistent with that documented in previous trials. |
| Conclusions: | The addition of bevacizumab to oxaliplatinbased chemotherapy significantly improved PFS in this firstline trial in patients with MCRC. Overall survival differences did not reach statistical significance, and response rate was not improved by the addition of bevacizumab. Treatment continuation until disease progression may be necessary in order to optimize the contribution of bevacizumab to therapy. |