Abstract
ABSTRACT Aim: Network meta-analysis (NMA) is used to compare treatment effects, taking all available evidence into account. This study describes a NMA of 1L treatments for stages IIIC and IV melanoma using the accelerated failure time (AFT) scale. The comparators were selected based on European clinical practice and included: dacarbazine (DTIC), DTIC + tamoxifen (TMX), temozolomide (TMZ), interferon (IFN), ipilimumab (IPI), vemurafenib (VM), dabrafenib (DB) and trametinib (TR). Reported outcomes were overall survival (OS) and progression-free survival (PFS). Methods: Studies in the systematic literature were identified through the Embase, Medline, and Cochrane databases. Kaplan-Meier curves were scanned, and individual patient level data were recreated using a published algorithm. Treatment effect estimates for each study were obtained using Cox proportional hazards (PH) and the AFT models. For the AFT, a generalized gamma distribution was assumed. Bayesian fixed-effects NMAs were conducted and assumed that treatment effects were comparable across trials. Results: Fourteen studies were identified and included in the analysis. Diagnostic tests results indicated that treatment effects were not constant over time in the PH model, and the AFT model better fit the trial data and, therefore, was used in the analysis. Studies using lower dose intensities of DTIC (800 mg/m2/d) were excluded due to heterogeneity. The inverse acceleration factors for OS and PFS for each treatment, compared with DTIC, are shown in the table (values lower than 1 indicate increased survival). Conclusions: VM is the only treatment that shows a statistically significant increase in both OS and PFS, compared with DTIC, when published RCT data are compared. Disclosure: C. Bexelius: I am an employee of F.Hoffmann-La Roche; J.M. Quigley: Consultant for Roche with compensation for conducting systematic review; P. Thuresson: I am an employee of F. Hoffmann-La Roche; N. Hawkins: I am employed by ICON PLC, a consultant to F. Hoffmann-La Roche. Table: 1095P . Inverse Acceleration Factor Compared With DTIC. Median (95% confidence interval) DB DB + TR 1mg DB + TR 2 mg DTIC + IFN DTIC + IFN + TMX DTIC + TMX IPI IPI + DTIC TMZ VM OS 0.86 (0.62,1.2) 0.87 (0.53,1.43) 0.7 (0.43,1.16) 1.13 (0.95,1.33) 3.35 (2.23,5.02) 3.53 (2.36,5.3) 1.05 (0.65,1.69) 0.77 (0.63,0.96) 0.97 (0.86,1.1) 0.74 (0.61,0.89) PFS 0.37 (0.29,0.46) 0.27 (0.19,0.38) 0.21 (0.15,0.29) 1.11 (0.89,1.38) 1.22 (0.85,1.75) 1.15 (0.8,1.65) 0.84 (0.7,1.02) - 0.91 (0.8,1.03) 0.32 (0.28,0.37)
Published Version
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