Entry Detail
| General information | |
| Database: | DB00968 |
| Objective: | In the BRIM3 trial, vemurafenib was associated with risk reduction versus dacarbazine of both death and progression in patients with advanced BRAF(V600) mutationpositive melanoma. they present an extended followup analysis of the total population and in the BRAF(V600E) and BRAF(V600K) mutation subgroups. |
| Authors: | McArthur GA,et al |
| Title: | Safety and efficacy of vemurafenib in BRAF(V600E) and BRAF(V600K) mutationpositive melanoma (BRIM3): extended followup of a phase 3, randomised, openlabel study. |
| Journal: | Lancet Oncol. |
| Year: | 2014 |
| PMID: | 24508103 |
| Trial Design | |
| Clinical Trial Id: | NCT01006980 |
| Agent: | vemurafenib |
| Target: | BRaf protooncogene serine/threonineprotein kinase |
| Cancer Type: | melanoma |
| Cancer Subtype: | BRAF V600mutant melanoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | extended followup of a phase III, randomised, openlabel study. |
| Key Patients Feature: | Patients older than 18 years, with treatmentnaive metastatic melanoma and whose tumour tissue was positive for BRAF(V600) mutations were eligible. Patients also had to have a life expectancy of at least 3 months, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and adequate haematological, hepatic, and renal function. |
| Biomarker: | BRAF(V600E) |
| Biomark Analysis: | For the 598 (91%) patients with BRAF(V600E) disease, median overall survival in the vemurafenib group was 13.3 months (95% CI 11.914.9) compared with 10.0 months (8.014.0) in the dacarbazine group (HR 0.75 [95% CI 0.600.93]; p=0.0085); median progression free survival was 6.9 months (95% CI 6.27.0) and 1.6 months (1.62.1), respectively (HR 0.39 [95% CI 0.330.47]; p<0.0001). For the 57 (9%) patients with BRAF(V600K) disease, median overall survival in the vemurafenib group was 14.5 months (95% CI 11.2not estimable) compared with 7.6 months (6.116.6) in the dacarbazine group (HR 0.43 [95% CI 0.210.90]; p=0.024); median progression free survival was 5.9 months (95% CI 4.49.0) and 1.7 months (1.42.9), respectively (HR 0.30 [95% CI 0.160.56]; p<0.0001). |
| Control Group Info: | single arm |
| Treatment Info: | Patients were randomly assigned by interactive voice recognition system to receive either vemurafenib (960 mg orally twice daily) or dacarbazine (1000 mg/m(2) of body surface area intravenously every 3 weeks). |
| Primary End Point: | overall survival and progression free survival, analysed in the intentiontotreat population (n=675), with data censored at crossover |
| Secondary End Point: | NA |
| Patients Number: | 675 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | 57% receiving vemurafenib and 9% of treated with dacarbazine. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | in the vemurafenib group vs in the dacarbazine group: 6.9 months [95% CI 6.17.0] vs 1.6 months [1.62.1]; HR 0.38 [95% CI 0.320.46]; p<0.0001). For the patients with BRAF(V600E) disease, median progression free survival was 6.9 months (95% CI 6.27.0) and 1.6 months (1.62.1), respectively (HR 0.39 [95% CI 0.330.47]; p<0.0001). For the patients with BRAF(V600K) disease, median progression free survival was 5.9 months (95% CI 4.49.0) and 1.7 months (1.42.9), respectively (HR 0.30 [95% CI 0.160.56]; p<0.0001). |
| Median OS A vs. C: | in the vemurafenib group vs in the dacarbazine group (13.6 months [95% CI 12.015.2] vs 9.7 months [7.912.8]; hazard ratio [HR] 0.70 [95% CI 0.570.87]; p=0.0008). For the patients with BRAF(V600E) disease, median overall survival in the vemurafenib group was 13.3 months (95% CI 11.914.9) compared with 10.0 months (8.014.0) in the dacarbazine group (HR 0.75 [95% CI 0.600.93]; p=0.0085); For the patients with BRAF(V600K) disease, median overall survival in the vemurafenib group was 14.5 months (95% CI 11.2not estimable) compared with 7.6 months (6.116.6) in the dacarbazine group (HR 0.43 [95% CI 0.210.90]; p=0.024); |
| Adverse Event(agent arm): | The most common grade 3 or 4 adverse events of interest in patients treated with vemurafenib were cutaneous squamouscell carcinomas, increased liver function tests, keratoacanthomas, rash, and arthralgia |
| Conclusions: | Inhibition of BRAF with vemurafenib improves survival in patients with the most common BRAF(V600E) mutation and in patients with the less common BRAF(V600K) mutation. |