An indirect treatment comparison of the efficacy of pembrolizumab versus competing regimens for the adjuvant treatment of stage III melanoma Maria Lorenzi Stella Arndorfer Raquel Aguiar-Ibañez Emilie Scherrer Frank Xiaoqing Liu Clemens Krepler 10.6084/m9.figshare.9114872.v1 https://tandf.figshare.com/articles/journal_contribution/An_indirect_treatment_comparison_of_the_efficacy_of_pembrolizumab_versus_competing_regimens_for_the_adjuvant_treatment_of_stage_III_melanoma/9114872 <p><b>Objective:</b> To determine the efficacy of pembrolizumab relative to other treatments used in stage III melanoma by conducting a systematic literature review (SLR) and network meta-analysis (NMA).</p> <p><b>Methods:</b> A SLR was conducted to identify randomized clinical trials (RCTs) evaluating approved adjuvant treatments including interferon-containing regimens, BRAF-inhibitors, and PD-L1 inhibitors in stage III melanoma patients. Relative treatment effects for recurrence-free survival (RFS) were synthesized with Bayesian NMA models that allowed for hazard ratios (HRs) to vary over time.</p> <p><b>Results:</b> Included studies formed a connected network of evidence composed of eight trials. In high-risk stage III patients, the HR for pembrolizumab vs observation decreased significantly over time with the superiority of pembrolizumab over observation becoming statistically meaningful before 3 months. By 9 months, the HR for pembrolizumab vs observation was statistically significantly lower than the HR for most other treatments vs observation, with the exception of ipilimumab and biochemotherapy due to overlapping 95% credible intervals. In BRAF + patients, pembrolizumab was statistically significantly better than observation after 3 months. The HR for both BRAF-inhibitors vs observation increased significantly over time and pembrolizumab was statistically superior to both BRAF-inhibitors after 15 months.</p> <p><b>Conclusions:</b> Pembrolizumab results in statistically significantly improved RFS compared to all competing regimens after 9 months, except ipilimumab and biochemotherapy, for the adjuvant treatment of stage III melanoma. However, point estimate HRs vs observation for pembrolizumab are much lower than those for ipilimumab. In BRAF + patients, the advantage of pembrolizumab versus competing interventions increases over time with respect to RFS.</p> 2019-07-26 11:10:52 Pembrolizumab immunotherapy PD-1 inhibitor adjuvant therapy melanoma indirect treatment comparison