Entry Detail
| General information | |
| Database: | DB00659 |
| Objective: | They investigated the BRAF kinase inhibitor vemurafenib in patients with advanced melanoma with symptomatic brain metastases. |
| Authors: | Dummer R, et al |
| Title: | Vemurafenib in patients with BRAF(V600) mutationpositive melanoma with symptomatic brain metastases: final results of an openlabel pilot study. |
| Journal: | Eur J Cancer. |
| Year: | 2014 |
| PMID: | 24295639 |
| Trial Design | |
| Clinical Trial Id: | NCT01253564 |
| Agent: | vemurafenib |
| Target: | BRaf protooncogene serine/threonineprotein kinase |
| Cancer Type: | advanced cancer with brain metastasis |
| Cancer Subtype: | brain metastases from BRAFV600 mutationpositivemelanoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | an openlabel, singlearm, twocentre, study |
| Key Patients Feature: | Eligible patients were older than 18 years and hadhistologically confirmed stage IV (American Joint Committee on Cancer staging criteria) metastatic melanomathat was BRAFV600 mutation positive; confirmed brainmetastases for which surgical resection was not a treatment option; and at least one previous failed treatmentfor brain metastases and required treatment with corticosteroids for symptom control (either a stable or adecreasing dose within 1 week of study entry). Patientscould have measurable or nonmeasurable diseaseaccording to Response Evaluation Criteria in SolidTumours, version 1.1 (RECIST 1.1). were to havean Eastern Cooperative Oncology Group performancestatus (ECOG PS) of 0-2, have recovered from thesideeffects of their most recent treatment for metastaticmelanoma, and have adequate haematological, renaland hepatic function. Evidence of progression of brainmetastases by magnetic resonance imaging (MRI) wasnot required prior to study entry. |
| Biomarker: | BRAF(V600) mutationpositive |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | vemurafenib (960mg twice a day) |
| Primary End Point: | safety |
| Secondary End Point: | best overall response rate, and progression free and overall survival. |
| Patients Number: | 24 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | An overall partial response (PR) at both intracranial and extracranial sites was achieved in 10 of 24 (42%; 95% CI, 22.163.4) evaluable patients, with stable disease in nine (38%; 95% CI, 18.859.4) patients. Of 19 patients with measurable intracranial disease, seven (37%) achieved >30% intracranial tumour regression, and three (16%; 95% CI, 3.439.6%) achieved a confirmed PR. |
| Disease Control Rate: | 0.8 |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 3.9 (95% CI, 3.0-5.5) months |
| Median OS A vs. C: | 5.3 (95% CI, 3.9-6.6) months |
| Adverse Event(agent arm): | Twentythree of 24 patients reported at least one adverse event (AE). Grade 3 AEs were reported in four (17%; 95% confidence interval [CI], 4.7-37.4%) patients and included cutaneous squamous cell carcinoma in four patients. |
| Conclusions: | Vemurafenib can be safely used in patients with advanced symptomatic melanoma that has metastasised to the brain and can result in meaningful tumour regression. |