Mekinist and selemetenib for uveal melanoma – pro
MEKINIST, in combination with dabrafenib, is indicated for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations, as detected by an FDA-approved test. There are studies of other MEk inhibitors for uveal melanoma but NCCN does not list Mekinist. A systemic review byDSteeb et al, however, found that, “UM is little responsive to MEK inhibition, regardless of the inhibiting agent and combination partner. Our results do not support the use of MEK inhibitors in UM. Novel treatment options are urgently needed in this patient population.” Selemetinib with dacarbazine found in a randomized study that the combination of selumetinib plus dacarbazine had a tolerable safety profile but did not significantly improve PFS compared with placebo plus dacarbazine. This result seems to supersede a study by Garvalhal that selumetinib compared with chemotherapy resulted in a modestly improved progression-free survival and response rate; however, no improvement in overall survival was observed. Improvement in clinical outcomes was accompanied by a high rate of adverse events. When concluded and published in 2018, the results were the same.
NCCN Uveal Melanoma UM-C, 1 2022
Carvajal RD, Sosman JA, Quevedo JF, Milhem MM, Joshua AM, Kudchadkar RR, Linette GP, Gajewski TF, Lutzky J, Lawson DH, Lao CD, Flynn PJ, Albertini MR, Sato T, Lewis K, Doyle A, Ancell K, Panageas KS, Bluth M, Hedvat C, Erinjeri J, Ambrosini G, Marr B, Abramson DH, Dickson MA, Wolchok JD, Chapman PB, Schwartz GK. Effect of selumetinib vs chemotherapy on progression-free survival in uveal melanoma: a randomized clinical trial. JAMA. 2014 Jun 18;311(23):2397-405. doi: 10.1001/jama.2014.6096. PMID: 24938562; PMCID: PMC4249701
Carvajal RD, Schwartz GK, Mann H, Smith I, Nathan PD. Study design and rationale for a randomised, placebo-controlled, double-blind study to assess the efficacy of selumetinib (AZD6244; ARRY-142886) in combination with dacarbazine in patients with metastatic uveal melanoma (SUMIT). BMC Cancer. 2015 Jun 10;15:467. doi: 10.1186/s12885-015-1470-z. PMID: 26059332; PMCID: PMC4460965..