Patients with advanced melanoma who were treated with the combination consisting of Taflinar (dabrafenib) plus Mekinist (trametinib) had a significantly improved survival rate at 3 years compared to those treated with Taflinar only. These results were presented at the 2016 annual meeting of the American Society of Clinical Oncology (ASCO).
Advanced melanoma refers to skin cancer that has spread from its site of origin to distant and/or several locations in the body. Historically, advanced melanoma had a poor outlook and only a small percentage of patients achieved long-term survival. However, recent treatments that have been targeted towards specific genetic mutations, as well as those that stimulate the immune system have resulted in significantly improved outcomes for patients with this disease.
Dabrafenib and trametinib are both agents referred to as kinase inhibitors. They block the action of certain biochemical pathways involved in the growth and spread of cancer cells.
They are both approved as single agents for the treatment of patients of melanoma that is advanced or is not able to be surgically removed. Treatment with dabrafenib as a single agent must be in patients whose melanoma has the BRAF V600E mutation as detected by an FDA-approved test. Treatment with trametinib as a single agent, as well as in combination with dabrafenib, must be in patients whose melanoma has the BRAF V600E or V600K mutations as detected by an FDA-approved test.
Updated results from a clinical trial referred to as the COMBI-d trial were recently presented at the 2016 ASCO meeting. The COMBI-d trial was a phase 3 trial that included 423 patients with advanced melanoma who had the BRAFV600E/K mutation(s). Approximately half of the patients were treated initially with dabrafenib (d) as a single agent, while the other half were treated with dabrafenib plus trametinib (d+t).
The updated results included a follow-up of 3 years.
- Survival was 44% for patients treated with d+t, versus 32% for those treated with d only.
- Survival without progression of cancer was 22% for patients treated with d+t, compared to 12% for those treated with d only
- Among the subgroup of patients with normal lactate dehydrogenase (LDH) levels, and fewer than 3 sites of cancer spread to distant sites, the survival rate at 3 years was 62% for those treated with d+t, compared with 45% for those treated with d only.
- No new safety concerns from treatment were identified.
The researchers concluded that the combination of dabrafenib plus trametinib provides superior overall survival at 3 years, compared to treatment with dabrafenib only among patients with advanced melanoma whose cancer is not able to be surgically treated, and whose cancer has the BRAF V600Eand K mutations. Further genetic analysis is ongoing among these patients.
Reference: Flaherty K, Davis M, Grob J J, et al. Genomic analysis and 3-y efficacy and safety update of COMBI-d: A phase 3 study of dabrafenib (D) + trametinib (T) vs D monotherapy in patients (pts) with unresectable or metastatic BRAF V600E/K-mutant cutaneous melanoma. Proceedings from the 2016 annual meeting of the American Society of Clinical Oncology. Abstract #9502. Available at: http://meetinglibrary.asco.org/content/168199-176. Accessed July 18, 2016.