Dabrafenib plus Trametinib versus Nivolumab in advanced melanoma
Patients
Patients with advanced melanoma
Intervention
Dabrafenib plus trametinib
Comparison
Nivolumab
Outcome
Absolute Effect
Certainty of evidence (GRADE)
Overall survival
The information compiled in four systematic reviews is contradictory, and all results have no statistical significance.One review [9] shows that the combination of dabrafenib and trametinib could increase the overall survival in patients (HR 0.87; CI 95% 0.45 - 1.68) when compared with nivolumab, the same as a second review [10] (HR 0.60; CI 95% 0.03 - 10.95).One review [11] shows that the combination of dabrafenib and trametinib could decrease the overall survival of patients (HR 1.21; CI95% 0.66 - 2.13) compared to nivolumab, the same result that four reviews [3] (HR 0.86; CI95% 0.57 - 1.24 in favor to nivolumab)
⊕◯◯◯1,2,3Very Low
Progression-free survival
Three reviews show that dabrafenib plus trametinib increase the progression-free survival of patients compared to nivolumab alone. (HR 0.33; CI 95% 0.19 - 0.58 [9]; HR 0.42; CI95% 0.20 - 0.77 [11]; and HR 2.00; CI95% 1.43-2.75 in favor of dabrafenib plus trametinib [3])
⊕◯◯◯1,3Very Low
Response to the treatment
One review [9] shows that nivolumab increases the proportion of patients that respond to the treatment (RR 3.08; CI 95% 1.47 - 6.45) compared to dabrafenib plus trametinib, and this result matches another review [10] (OR 5.96; CI 95% 1.88 - 29.25)
⊕◯◯◯1,2,3Very Low
Toxicity
Two reviews show that dabrafenib plus trametinib has more serious adverse events compared to nivolumab (RR 1.69; CI 95% 0.45 – 6.59 [11] and RR 1.60; CI 95% 1.04 – 2.49 [12]).Two reviews show that dabrafenib plus trametinib has more grade III or IV adverse events (RR 2.17; CI 95% 1.27 – 3.73 [9] and RR 0.59; CI95% 0.35 - 0.93 in favor of nivolumab [3]).
⊕◯◯◯1,3Very Low
Health-related quality of Life
In one review [11], the authors stated that the health-related quality of life could not be reported because the network meta-analysis was not performed due to the poor available information. The other reviews [3,9,10,14] did not evaluate this outcome.
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Margin of error: 95% confidence interval (CI).HR: Hazard Ratio.OR: Odds RatioRR: Risk RatioGRADE: Evidence grades of the GRADE Working Group (see later).1 The certainty of the evidence was downgraded by one level for risk of bias due to some trials including incomplete data, or other biases like crossover, in their network meta-analysis.2 The certainty of the evidence was downgraded by one level for the imprecision of the results due to the margin of error, going through the no-effect threshold3 The certainty of the evidence was downgraded by two levels for indirect evidence due to the results coming from a network meta-analysis. ,
