Selumetinib is an orally available selective, non-ATP-competitive inhibitor of MEK1/2. On the basis of preclinical data, this phase II study aimed to investigate the effectiveness and safety of selumetinib combined with dacarbazine as first-line treatment of BRAF-mutant advanced cutaneous or unknown primary melanoma.
Ninety-one patients were randomised to dacarbazine, either in combination with selumetinib (n=45) or placebo (n=46). The authors reported that overall survival did not differ significantly between groups (median 13.9 months, 80% CI 10.2—15.6, in the selumetinib plus dacarbazine group and 10.5 months, 9.6—14.7, in the placebo plus dacarbazine group; hazard ratio [HR] 0.93, 80% CI 0.67—1.28, one-sided p=0.39). However, progression-free survival was significantly improved in the selumetinib plus dacarbazine group versus the placebo plus dacarbazine group (HR 0.63, 80% CI 0.47—0.84, one-sided p=0.021), with a median of 5.6 months (80% CI 4.9—5.9) versus 3.0 months (2.8—4.6), respectively. The incidence of grade 3 or higher and serious adverse events was higher in the selumetinib plus dacarbazine group compared with the placebo plus dacarbazine group, as was discontinuation of selumetinib because of adverse events
Two effective drugs, the BRAF inhibitor vemurafenib and the CTLA4-blocking monoclonal antibody ipilimumab were licensed whilst this study was ongoing. Vemurafenib is recommended by NICE for the treatment of BRAF-600 mutation positive unresectable or metastatic melanoma if the manufacturer provides vemurafenib with the discount agreed in the patient access scheme. Ipilimumab is recommended by NICE as an option for treating advanced (unresectable or metastatic) melanoma in people who have received prior therapy, if the manufacturer provides ipilimumab with the discount agreed in the patient access scheme.