| General information |
| Database: | DB00717 |
| Objective: | To compare the efficacy of cediranib (a vascular endothelial growth factor receptor tyrosine kinase inhibitor [VEGFR TKI]) with that of bevacizumab (antiVEGFA monoclonal antibody) in combination with chemotherapy as firstline treatment for advanced metastatic colorectal cancer (mCRC). |
| Authors: | Schmoll HJ, et al |
| Title: | Cediranib with mFOLFOX6 versus bevacizumab with mFOLFOX6 as firstline treatment for patients with advanced colorectal cancer: a doubleblind, randomizedphase III study (HORIZON III). |
| Journal: | J Clin Oncol. |
| Year: | 2012 |
| PMID: | 22965961 |
| Trial Design |
| Clinical Trial Id: | NCT00384176 |
| Agent: | Cediranib bevacizumab
|
| Target: | NA
|
| Cancer Type: | colorectal cancer |
| Cancer Subtype: | advanced colorectal cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Cediranib+mFOLFOX6 ;bevacizumab+mFOLFOX6 |
| Study Type: | phase II/III, randomized, doubleblind, adaptive design study |
| Key Patients Feature: | Eligible patients were age 18 years with histologic or cytologic confirmation of mCRC (stage IV), a WHO performance status (PS) of 0 or 1, and lifeexpectancy 12 weeks. Any adjuvant or neoadjuvant oxaliplatin or FU therapy must have been completed more than 12 or more than 6 months, respectively, before study entry. Exclusion criteria included any unresolved toxicityof Common Toxicity Criteria (CTC) grade 2 from previous anticancertherapy (except hematologic toxicity and alopecia) and prior therapy withmonoclonal antibodies or smallmolecule inhibitors against VEGF and VEGFRs. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | Cediranib with mFOLFOX6 versus bevacizumab with mFOLFOX6 |
| Treatment Info: | Patients randomly assigned 1:1:1 received mFOLFOX6 [oxaliplatin 85 mg/m(2) and leucovorin 400 mg/m(2) intravenously followed by fluorouracil 400 mg/m(2) intravenously on day 1 and then continuous infusion of 2, 400 mg/m(2) over the next 46 hours every 2 weeks] with cediranib (20 or 30 mg per day) or bevacizumab (5 mg/kg every 14 days). An independent endofphase II analysis concluded that mFOLFOX6/cediranib 20 mg met predefined criteria for continuation; subsequent patients received mFOLFOX6/cediranib 20 mg or mFOLFOX6/bevacizumab (randomly assigned 1:1). |
| Primary End Point: | the efficacy of cediranib 20 mg plus mFOLFOX6 compared with bevacizumab plus mFOLFOX6 by assessment of PFS. |
| Secondary End Point: | comparisons between the two treatment arms for OS, objective response rate , duration of response (DoR), safety and tolerability, rate of resection of liver metastases (all patients with liver metastases at baselineincluded), and the effects on healthrelated quality of life. Exploratory end points included assessments of tumor and bloodbased biomarkers, the resultsof which will be reported separately. |
| Patients Number: | 1422 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 9.9 months (cediranib 20 mg) and 10.3 months (bevacizumab). |
| Median OS A vs. C: | 22.8 months with cediranib versus 21.3 months with bevacizumab. |
| Adverse Event(agent arm): | Common adverse events with more than 5% incidence in the cediranib arm included diarrhea, neutropenia, and hypertension. Cediranibtreated patients completed fetheyr chemotherapy cycles than bevacizumabtreated patients (median 10 v 12 cycles). |
| Conclusions: | Cediranib activity, in terms of PFS and OS, was comparable to that of bevacizumab when added to mFOLFOX6; hotheyver, the predefined boundary for PFS noninferiority was not met. The cediranib safety profile was consistent with previous studies but led to less favorable PROs compared with bevacizumab. Investigation of oral TKIs in CRC continues. |