| General information |
| Database: | DB00181 |
| Objective: | Dabrafenib, a selective BRAF inhibitor, has shown activity with a manageable safety profile inphase I/II studies in patients (pts) with BRAFV600Emutated metastatic melanoma (MM). Thisphase III trial compared progression free survival (PFS) in pts with advanced MM treated either with dabrafenib or dacarbazine (DTIC). TITLE:Phase III, randomized, openlabel, multicenter trial (BREAK3) comparing the BRAF kinase inhibitor dabrafenib (GSK2118436) with dacarbazine (DTIC) in patients with BRAFV600Emutated melanoma |
| Authors: | Hauschild A, et al |
| Title: | Phase III, randomized, openlabel, multicenter trial (BREAK3) comparing the BRAF kinase inhibitor dabrafenib (GSK2118436) with dacarbazine (DTIC) in patients with BRAFV600Emutated melanoma |
| Journal: | Journal of Clinical Oncology |
| Year: | 2012 |
| PMID: | http://meeting.ascopubs.org/cgi/content/abstract/30/18_suppl/LBA8500 |
| Trial Design |
| Clinical Trial Id: | NCT01227889 |
| 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 phase III, randomized, openlabel, multicenter trial (BREAKIII) |
| Key Patients Feature: | Pts with previously untreated, unresectable stage III or IV BRAFV600Emutated melanoma at 93 centers globally:Median age was 52 years, 31% of pts were ECOG >1, 66% M1c, 33% LDH > ULN. |
| Biomarker: | BRAF V600Emutated |
| Biomark Analysis: | NA |
| Control Group Info: | dacarbazine (DTIC) |
| Treatment Info: | Pts were randomized (3:1) and stratified by stage to dabrafenib (150 mg po bid) or DTIC (1000 mg/m2, IV, q3w). |
| Primary End Point: | PFS |
| Secondary End Point: | PFS by IR, overall survival (OS), response rate (RR), duration of response, safety and pharmacokinetics. |
| Patients Number: | 250 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | Confirmed RR was 53% for dabrafenib and 19% for DTIC. Benefits in RR were observed in all subgroups evaluated. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | The hazard ratio for PFS was 0.30 (95% CI: 0.180.53; p < 0.0001). Median PFS was 5.1 months for dabrafenib and 2.7 for DTIC.Benefits in PFS were observed in all subgroups evaluated. |
| Median OS A vs. C: | OS data were immature, with 30 deaths reported. |
| Adverse Event(agent arm): | Common adverse events (AEs) on the dabrafenib arm were hyperkeratosis (37%), headache (32%), pyrexia (28%), arthralgia (27%), skin papillomas (24%). Serious AEs (> 1%) on the dabrafenib arm included pyrexia (4%), squamous cell carcinomas (6%), and new primary melanomas (2%). |
| Conclusions: | Dabrafenib demonstrated a significant improvement in PFS and ORR over DTIC with an acceptable safety profile. |