In a nutshell
This phase II trial evaluated the efficacy and safety of selumetinib in combination with docetaxel (Taxotere) as first-line treatment for patients diagnosed with advanced melanoma.
Some background
Despite recent advances in targeted biological agents for the treatment of BRAF-mutated melanoma, treatment options for wild-type BRAF melanoma patients remain limited. Selumetinib is a new targeted therapy for melanoma, a MEK-inhibitor, which has been shown to suppress cell grows independent of genetic mutation status. Pre-clinical trials with selumetinib also demonstrated increased drug efficacy when employed in combination with chemotherapy such as docetaxel.
Methods & findings
This early phase trial included 83 patients diagnosed with wild-type BRAF advanced melanoma. 41 patients were randomly assigned to receive six cycles of docetaxel in combination with selumetinib, while 42 patients were assigned to receive docetaxel plus a placebo.
32% of patients receiving docetaxel plus selumetinib showed good response to treatment as opposed to only 14% of patients receiving docetaxel plus a placebo. The average progression free survival was 4.23 months among patients receiving docetaxel plus selumetinib and 3.93 months in those receiving the placebo. However, this difference was deemed statistically insignificant on further analysis. In addition, patients in the selumetinib group reported more serious adverse events, with 45% of patients requiring a docetaxel dose reduction, compared to only 20% in the control group.
The bottom line
This early phase trial demonstrated increased rates of response to selumetinib treatment among wild-type melanoma patients. However, no significant difference was noted in progression free survival, and significant safety concerns arise from its combination with docetaxel chemotherapy.
Published By :
Annals of oncology
Date :
Feb 24, 2014
