Efficacy and Safety of Selumetinib Compared with Current Therapies for Advanced Cancer: a Meta-analysis

Background and Aim: Selumetinib is a promising and interesting targeted therapy agent as it may reverseradioiodine uptake in patients with radioiodine-refractory differentiated thyroid cancer. We conduct this metaanalysisto compare the efficacy and safety of selumetinib with current therapies in patients with advancedcancer.
Methods: An electronic search was conducted using PubMed/ Medicine, EMBASE and Cochrane librarydatabases. Statistical analyses were carried out using either random-effects or fixed-effects models according tothe heterogeneity of eligible studies.
Results: Six eligible trials involved 601 patients were identified. Comparedwith current therapies, treatment schedules with selumetinib did not improve progression free survival (hazardratio, 0.91; 95%CI 0.70–1.17, P= 0.448), but did identify better clinical benefits (odds ratio, 1.24; 95%CI 0.69–2.24, P = 0.472) and less disease progression (hazard ratio, 0.72; 95%CI 0.51–1.00, P = 0.052) though its impactwas not statistically significant. Sub-group analysis resulted in significantly improved progression free survival(hazard ratio, 0.61; 95%CI 0.49–0.57, P = 0.00), clinical benefits (odds ratio, 3.04; 95%CI 1.60–5.77, P = 0.001)and reduced disease progression (hazard ratio, 0.35; 95%CI 0.18–0.67, P = 0.001) in patients administratedselumetinib. Dermatitis acneiform (risk ratio, 9.775; 95%CI 3.143–30.395, P = 0.00) and peripheral edema (riskratio, 2.371; 95%CI 1.690–3.327, P = 0.00) are the most frequently observed adverse effects associated withselumetinib.
Conclusions: Compared with current chemotherapy, selumetinib has modest clinical activity asmonotherapy in patients with advanced cancer, but combinations of selumetinib with cytotoxic agents in patientswith BRAF or KRAS mutations hold great promise for cancer treatment. Dermatitis acneiform and peripheraledema are the most frequently observed adverse effects in patients with selumetinib.