| General information |
| Database: | DB00040 |
| Objective: | Docetaxel plus prednisone is standard firstline chemotherapy for men with metastatic castrateresistant prostate cancer. Aflibercept is a recombinant human fusion protein that binds A and B isoforms of VEGF and placental growth factor, thereby inhibiting angiogenesis. They assessed whether the addition of aflibercept to docetaxel and prednisone would improve overall survival in men with metastatic castrateresistant prostate cancer compared with the addition of placebo to docetaxel and prednisone. |
| Authors: | Tannock IF, et al |
| Title: | Aflibercept versus placebo in combination with docetaxel and prednisone for treatment of men with metastatic castrationresistant prostate cancer (VENICE): a phase 3, doubleblind randomised trial. |
| Journal: | Lancet Oncol. |
| Year: | 2013 |
| PMID: | 23742877 |
| Trial Design |
| Clinical Trial Id: | NCT00519285 |
| Agent: | aflibercept
|
| Target: | VEGFA, vascular endothelial growth factor B, PIGF
|
| Cancer Type: | prostate cancer |
| Cancer Subtype: | advanced castrationresistant prostate cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Aflibercept+ docetaxel+prednisone |
| Study Type: | a phase III, multicentre, randomised doubleblind placebocontrolled parallel group study done in IIII countries (I87 sites)(VENICE) |
| Key Patients Feature: | Men with metastatic castrateresistant prostate cancer, adequate organ function, and no prior chemotherapy |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | placebo+docetaxel and prednisone |
| Treatment Info: | patients were treated with docetaxel (75 mg/m(2) intravenously every 3 weeks) and oral prednisone (5 mg twice daily) and randomly allocated (1:1) to receive aflibercept (6 mg/kg) or placebo, intravenously, every 3 weeks. Treatment allocation was done centrally via an interactive voice response system, using a computergenerated sequence with a permutedblock size of four and stratified according Eastern Cooperative Group performance status (01 vs 2). Patients, investigators, and other individuals responsible for study conduct and data analysis were masked to treatment assignment. Aflibercept or placebo vials were supplied in identical boxes. |
| Primary End Point: | overall survival using intentiontotreat analysis |
| Secondary End Point: | NA |
| Patients Number: | 1224 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | 873 men had died. Median overall survival was 22.1 months (95.6% CI 20.324.1) in the aflibercept group and 21.2 months (19.623.8) in the placebo group (stratified hazard ratio 0.94, 95.6% CI 0.821.08; p=0.38). |
| Adverse Event(agent arm): | a higher incidence of grade 34 gastrointestinal disorders (182 [30%] vs 48 [8.0%]), haemorrhagic events (32 [5.2%] vs ten [1.7%]), hypertension (81 [13%] vs 20 [3.3%]), fatigue (97 [16%] vs 46 [7.7%]), infections (123 [20%] vs 60 [10%]) and treatmentrelated fatal adverse events (21 [3.4%] vs nine [1.5%]) in the aflibercept group than in the placebo group was recorded. |
| Conclusions: | Aflibercept in combination with docetaxel and prednisone given as firstline chemotherapy for men with metastatic castrateresistant prostate cancer resulted in no improvement in overall survival and added toxicity compared with placebo. Docetaxel plus prednisone remains the standard treatment for such men who need firstline chemotherapy. |