Indirect Comparison of Combined BRAF and MEK Inhibition in Melanoma Patients with Elevated Baseline Lactate Dehydrogenase
Valerie Glutsch, Teresa Amaral, Claus Garbe, Kai-Martin Thoms, Peter Mohr, Axel Hauschild, Bastian Schilling
DOI: 10.2340/00015555-3526
Abstract
The approval of BRAF and MEK inhibitors has significantly improved treatment outcomes for patients with BRAF-mutated metastatic melanoma. The 3 first-line targeted therapy trials have provided similar results, and thus the identification of predictive biomarkers may generate a more precise basis for clinical decision-making. Elevated baseline lactate dehydrogenase (LDH) has already been determined as a strong prognostic factor. Therefore, this indirect analysis compared subgroups with elevated baseline LDH across the pivotal targeted therapy trials co-BRIM, COMBI-v and COLUMBUS part 1. The Bucher method was used to compare progression-free survival, objective response rate and overall survival indirectly. The results show a non-significant risk reduction for progression in the subgroup with elevated baseline LDH receiving vemurafenib plus cobimetinib compared with dabrafenib plus trametinib and encorafenib plus binimetinib. Although an indirect comparison, these data might provide some guidance for treatment recommendations in melanoma patients with elevated LDH.
Significance
Targeted therapy has significantly improved the prognosis of patients with BRAF-mutated metastatic melanoma. Since there are 3 different targeted therapy regimes available, the identification of predictive factors may generate a more precise basis for clinical decision-making. An increased level of lactate dehydrogenase has been determined as a strong prognostic factor. Therefore, the aim of this study was to determine if approved targeted therapy regimes differ significantly in terms of efficacy in patients with elevated lactate dehydrogenase. The study used the Bucher method to indirectly compare the outcome of melanoma patients with elevated lactate dehydrogenase across the pivotal trials co-BRIM, COMBI-v and COLUMBUS part 1.
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