| General information |
| Database: | DB00221 |
| Objective: | Ipilimumab is a fully human monoclonal antibody that binds cytotoxic Tlymphocyte antigen 4 to enhance antitumour immunity. Their aim was to assess the use of ipilimumab after radiotherapy in patients with metastatic castrationresistant prostate cancer that progressed after docetaxel chemotherapy. |
| Authors: | Kwon ED, et al |
| Title: | Ipilimumab versus placebo after radiotherapy in patients with metastatic castrationresistant prostate cancer that had progressed after docetaxel chemotherapy (CA184043): a multicentre, randomised, doubleblind, phase 3 trial. |
| Journal: | Lancet Oncol |
| Year: | 2014 |
| PMID: | 24831977 |
| Trial Design |
| Clinical Trial Id: | NCT00861614 |
| Agent: | ipilimumab
|
| Target: | Cytotoxic Tlymphocyte antigen 4 (CTLA4)
|
| Cancer Type: | prostate cancer |
| Cancer Subtype: | advanced castrationresistant prostate cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a multicentre, randomised, doubleblind, phase III trial |
| Key Patients Feature: | men with at least one bone metastasis from castrationresistant prostate cancer that had progressed after docetaxel treatment done in 191 centres across 26 countries |
| Biomarker: | alkaline phosphatase concentration, haemoglobin concentration |
| Biomark Analysis: | Serum prostatespecific antigen levels were prospectively monitored as a biomarker for cancer activity. |
| Control Group Info: | placebo |
| Treatment Info: | pts were randomly assigned in a 1:1 ratio to receive bonedirected radiotherapy (8 Gy in one fraction) follotheyd by either ipilimumab 10 mg/kg or placebo every 3 weeks for up to four doses. Nonprogressing patients could continue to receive ipilimumab at 10 mg/kg or placebo as maintenance therapy every 3 months until disease progression, unacceptable toxic effect, or death. Patients were randomly assigned to either treatment group via a minimisation algorithm, and stratified by ECOG performance status, alkaline phosphatase concentration, haemoglobin concentration, and investigator site. Patients and investigators were masked to treatment allocation. |
| Primary End Point: | overall survival |
| Secondary End Point: | NA |
| Patients Number: | 799 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | median 4.0 [95% CI 3.6-4.3] vs 3.1 [2.9-3.4] months; HR 0.70, 95% CI 0.61-0.82; p<0.0001; |
| Median OS A vs. C: | Median OS was 11.2 months (95% CI 9.512.7) with ipilimumab and 10.0 months (8.311.0) with placebo (hazard ratio [HR] 0.85, 0.721.00; p=0.053).however, the assessment of the proportional hazards assumption showed that it was violated (p=0.0031). A piecewise hazard model showed that the HR changed over time: the HR for 05 months was 1.46 (95% CI 1.101.95), for 512 months was 0.65 (0.500.85), and beyond 12 months was 0.60 (0.430.86). |
| Adverse Event(agent arm): | The most common grade 34 adverse events were immunerelated, occurring in 101 (26%) patients in the ipilimumab group and 11 (3%) of patients in the placebo group. The most frequent grade 34 adverse events included diarrhoea (64 [16%] of 393 patients in the ipilimumab group vs seven [2%] of 396 in the placebo group), fatigue (40 [11%] vs 35 [9%]), anaemia (40 [10%] vs 43 [11%]), and colitis (18 [5%] vs 0). Four (1%) deaths occurred because of toxic effects of the study drug, all in the ipilimumab group. |
| Conclusions: | Although there was no significant difference bettheyen the ipilimumab group and the placebo group in terms of overall survival in the primary analysis, there were signs of activity with the drug that warrant further investigation. |