Entry Detail
| General information | |
| Database: | DB00175 |
| Objective: | The orally available BRAF kinase inhibitor vemurafenib, compared with dacarbazine, shows improved response rates, progression free survival (PFS), and overall survival in patients with metastatic melanoma that has a BRAF(V600) mutation. They assessed vemurafenib in patients with advanced metastatic melanoma with BRAF(V600) mutations who had few treatment options. |
| Authors: | Larkin J, et al |
| Title: | Vemurafenib in patients with BRAF(V600) mutated metastatic melanoma: an openlabel, multicentre, safety study. |
| Journal: | N Engl J Med. |
| Year: | 2014 |
| PMID: | 24582505 |
| Trial Design | |
| Clinical Trial Id: | NCT01307397 |
| Agent: | vemurafenib |
| Target: | BRaf protooncogene serine/threonineprotein kinase |
| Cancer Type: | melanoma |
| Cancer Subtype: | advanced BRAF(V600E/K) mut(+) melanoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | an openlabel, phase III, multicentre study |
| Key Patients Feature: | patients with untreated or previously treated melanoma and a BRAF(V600) mutation in 44 countries |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | dacarbazine |
| Treatment Info: | patients with untreated or previously treated melanoma and a BRAF(V600) mutation received oral vemurafenib 960 mg twice a day. |
| Primary End Point: | safety |
| Secondary End Point: | NA |
| Patients Number: | 3226 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | not mentioned |
| Disease Control Rate: | At data cutoff, 868 (27%) patients were on study treatment and 2354 (73%) had withdrawn, mainly because of disease progression. |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Common adverse events of all grades included rash (1592 [49%]), arthralgia (1259 [39%]), fatigue (1093 [34%]), photosensitivity reaction (994 [31%]), alopecia (826 [26%]), and nausea (628 [19%]). 1480 (46%) patients reported grade 3 or 4 adverse events, including cutaneous squamous cell carcinoma (389 [12%]), rash (155 [5%]), liver function abnormalities (165 [5%]), arthralgia (106 [3%]), and fatigue (93 [3%]). Grade 3 and 4 adverse events were reported more frequently in patients aged 75 years and older (n=257; 152 [59%, 95% CI 5365] and ten [4%, 27], respectively) than in those younger than 75 years (n=2965; 1286 [43%, 4245] and 82 [3%, 23], respectively). |
| Conclusions: | Vemurafenib safety in this diverse population of patients with BRAF(V600) mutated metastatic melanoma, who are more representative of routine clinical practice, was consistent with the safety profile shown in the pivotal trials of this drug. |