BackgroundMetastatic melanoma is an aggressive form of skin cancer with a high mortality rate and the fastest growing global incidence rate of all malignancies. The introduction of BRAF/MEK inhibitor combinations has yielded significant increases in PFS and OS for melanoma. However, at present, no direct comparisons between different BRAF/MEK combinations have been conducted. In light of this, an indirect treatment comparison was performed between two BRAF/MEK inhibitor combination therapies for metastatic melanoma, dabrafenib plus trametinib and vemurafenib plus cobimetinib, in order to understand the relative efficacy and toxicity profiles of these therapies.MethodsA systematic literature search identified two randomized trials as suitable for indirect comparison: the coBRIM trial of vemurafenib plus cobimetinib versus vemurafenib and the COMBI-v trial of dabrafenib plus trametinib versus vemurafenib. The comparison followed the method of Bucher et al. and analyzed both efficacy (overall survival [OS], progression-free survival [PFS], and overall response rate [ORR]) and safety outcomes (adverse events [AEs]).ResultsThe indirect comparison revealed similar efficacy outcomes between both therapies, with no statistically significant difference between therapies for OS (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.68 − 1.30), PFS (HR 1.05, 95% CI 0.79 − 1.40), or ORR (risk ratio [RR] 0.90, 95% CI 0.74 − 1.10). Dabrafenib plus trametinib differed significantly from vemurafenib plus cobimetinib with regard to the incidence of treatment-related AE (RR 0.92, 95% CI 0.87 − 0.97), any AE grade ≥3 (RR 0.71, 95% CI 0.60 − 0.85) or dose interruption/modification (RR 0.77, 95% CI 0.60 − 0.99). Several categories of AEs occurred significantly more frequently with vemurafenib plus cobimetinib, while some occurred significantly more frequently with dabrafenib plus trametinib. For severe AEs (grade 3 or above), four occurred significantly more frequently with vemurafenib plus cobimetinib and no severe AE occurred significantly more frequently with dabrafenib plus trametinib.ConclusionsThis indirect treatment comparison suggested that dabrafenib plus trametinib had comparable efficacy to vemurafenib plus cobimetinib but was associated with reduced adverse events.

Changes in body weight, liver weight, liver glycogen, blood plasma pH, hematocrit, plasma protein, and glucose levels in the Atlantic cod (Gadus morhua L.) during feeding, fasting, and liver regeneration are recorded. Resting liver glycogen content (37 ± 7 mg/100 g liver) is much lower than in many terrestrial and freshwater vertebrates. There is a transient increase in liver glycogen (702 ± 188 mg/100 g liver) with resumed feeding after prolonged fasting. Average resting levels of plasma protein (4.66 ± 0.36% w/v), glucose (100 ± 4 mg/100 ml plasma) and hematocrit (23.2 ± 1.2% v/v) decreased during the initial stages of food depletion. A reversal of this trend resulting in apparent increased levels is observed in acute malnutrition. This is attributed to dehydration of plasma with consequent drop in the total blood volume. The steady increase in plasma pH (7.24–7.54) with the duration of fasting may be due to extensive deamination of tissue protein amino acids for gluconeogenesis.

Background: Metastatic melanoma is an aggressive form of skin cancer with a high mortality rate and the fastest growing global incidence rate of all malignancies. The introduction of BRAF/MEK inhibitor combinations has yielded significant increases in PFS and OS for melanoma. However, at present, no direct comparisons between different BRAF/MEK combinations have been conducted. In light of this, an indirect treatment comparison was performed between two BRAF/MEK inhibitor combination therapies for metastatic melanoma, dabrafenib plus trametinib and vemurafenib plus cobimetinib, in order to understand the relative efficacy and toxicity profiles of these therapies. Several categories of AEs occurred significantly more frequently with vemurafenib plus cobimetinib, while some occurred significantly more frequently with dabrafenib plus trametinib. For severe AEs (grade 3 or above), four occurred significantly more frequently with vemurafenib plus cobimetinib and no severe AE occurred significantly more frequently with dabrafenib plus trametinib. Conclusions: This indirect treatment comparison suggested that dabrafenib plus trametinib had comparable efficacy to vemurafenib plus cobimetinib but was associated with reduced adverse events.

Current data suggest that melanoma-related HCRU (hospice visits and hospitalization) is lower among ipilimumab patients than those receiving other approved treatments. Future analyses will present data for longer follow up and larger sample size.

Current data suggest that melanoma-related HCRU (hospice visits and hospitalization) is lower among ipilimumab patients than those receiving other approved treatments. Future analyses will present data for longer follow up and larger sample size.