| General information |
| Database: | DB00182 |
| Objective: | This multicenter, singlearm, phase II study assessed the safety and clinical activity of dabrafenib in BRAF(V600E/K) mutationpositive metastatic melanoma (mut(+) MM). |
| Authors: | Ascierto PA, et al |
| Title: | Phase II trial (BREAK2) of the BRAF inhibitor dabrafenib (GSK2118436) in patients with metastatic melanoma. |
| Journal: | J Clin Oncol. |
| Year: | 2013 |
| PMID: | 23918947 |
| Trial Design |
| Clinical Trial Id: | NCT01153763 |
| Agent: | dabrafenib
|
| 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: | a multicenter, singlearm, phase II study |
| Key Patients Feature: | Histologically confirmed patients with stage IV BRAF(V600E/K) mut(+) MM. Seventysix patients with BRAF(V600E) and 16 patients with BRAF(V600K) mut(+) MM |
| Biomarker: | Baseline cfDNA levels /BRAF(V600E) mut(+) |
| Biomark Analysis: | Baseline cfDNA levels predicted response rate and PFS in BRAF(V600E) mut(+) MM patients. |
| Control Group Info: | single arm |
| Treatment Info: | Pts received oral dabrafenib 150 mg twice daily until disease progression, death, or unacceptable adverse events (AEs). |
| Primary End Point: | investigatorassessed overall response rate in BRAF(V600E) mut(+) MM patients. |
| Secondary End Point: | progression free survival (PFS) and overall survival (OS). Exploratory objectives included the comparison of BRAF mutation status between tumorspecific circulating cellfree DNA (cfDNA) and tumor tissue, and the evaluation of cfDNA as a predictor of clinical outcome. |
| Patients Number: | 92 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | In the BRAF(V600E) group, 45 patients (59%) had a confirmed response (95% CI, 48.2 to 70.3), including five patients (7%) with complete responses. Two patients (13%) with BRAF(V600K) mut(+) MM had a confirmed partial response (95% CI, 0 to 28.7). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | In the BRAF(V600E) and BRAF(V600K) groups, median PFS was 6.3 months and 4.5 months |
| Median OS A vs. C: | In the BRAF(V600E) and BRAF(V600K) groups, median OS was 13.1 months and 12.9 months, respectively |
| Adverse Event(agent arm): | The most common AEs were arthralgia (33%), hyperkeratosis (27%), and pyrexia (24%). Overall, 25 patients (27%) experienced a serious AE and nine patients (10%) had squamous cell carcinoma. |
| Conclusions: | Dabrafenib was well tolerated and clinically active in patients with BRAF(V600EK) mut(+) MM. cfDNA may be a useful prognostic and response marker in future studies. |