There was no difference in health-related quality of life among patients with resected stage III melanoma with BRAF mutations treated with adjuvant dabrafenib plus trametinib and those assigned to placebo, according to a patient-reported outcomes analysis of the COMBI-AD study.
“Our findings provide evidence that adjuvant dabrafenib plus trametinib did not have any substantial effect on patient health-related quality of life,” wrote Dirk Schadendorf, MD, of University Hospital Essen in Germany, and colleagues, in Lancet Oncology. “Furthermore, there was a substantial decrease in health-related quality of life after disease recurrence, highlighting the benefit to patients of remaining relapse-free and supporting the use of dabrafenib plus trametinib on the basis of a significant improvement in relapse-free survival in the primary analysis.”
The phase III COMBI-AD study found that combination adjuvant treatment with dabrafenib plus trametinib significantly improved relapse-free survival at 3 years in patients with resected stage III melanoma with BRAF V600E or BRAF V600K mutations.
In this analysis, Schadendorf and colleagues evaluated health-related quality of life using the European Quality of Life 5-Dimensions 3-Levels (EQ-5D-3L) questionnaire, which assesses five functional domains: mobility, self-care, usual activities, pain or discomfort, and anxiety or depression. Outcomes were assessed at baseline and every 3 months during treatment. If patients discontinued treatment, the assessment was also given at that time.
During the 12-month treatment phase of the trial, there was no significant or clinically meaningful difference between the two study arms in health-related quality of life, as assessed by EQ-5D-3L.
At disease recurrence, there was a significant decrease in visual analog scale scores—which allowed patients to rate their current health from 0 to 100—in both the adjuvant therapy group (P = .0032) and the placebo group (P < .0001).
“These findings are consistent with those from patients with metastatic melanoma, in whom disease progression is associated with deterioration in patient-reported outcomes, regardless of treatment received,” the researchers wrote.
Similarly, there were also decreases in utility scores at disease recurrence for dabrafenib plus trametinib (P < .0001) and placebo (P < .0001).
The researchers acknowledged some limitations to the analysis.
“In the assessment of the effect of adverse events on EQ-5D-3L scores, patients were divided according to whether they had the adverse event at any time during the treatment phase; thus, patients might not have been experiencing an adverse event at the time of the assessments and this could lead to recall bias,” they wrote. “Additionally, selection bias might have influenced these findings, because patients with the most detriment to health might have withdrawn early from the study and therefore might not be captured in later assessments.”
In an editorial that accompanied the study, B. Mark Smithers, of the University of Queensland in Australia, wrote that the results of this trial together with the results of two adjuvant therapy trials looking at ipilimumab and the combination of ipilimumab plus nivolumab “are likely to affect the future treatment” of patients with resected stage III melanoma with BRAF mutations.
Although none of these trials were designed to evaluate health-related quality of life, Smithers noted, patients treated with dabrafenib plus trametinib can be reassured “that if they have an adverse event or have ceased therapy that they are likely to return to a satisfactory functioning level.”
“In COMBI-AD, the absence of a detrimental effect on longer-term health-related quality of life, if the disease does not recur, is also reassuring,” Smithers wrote. “For immunotherapy trials, patients can be offered similar counselling related to recovery after adverse events and at the end of the treatment, although in these trials, the longer-term impact on health-related quality of life is awaited.”