Patient-Reported Outcomes in the COMBI-AD Trial


Key Points

  • No significant differences in patient-reported outcomes were observed during treatment or follow-up.
  • Worsening in patient-reported outcomes occurred in both groups at disease recurrence.  

In a study focused on the phase III COMBI-AD trial reported in The Lancet Oncology, Schadendorf et al found no difference in patient-reported outcomes with adjuvant dabrafenib plus trametinib vs placebo in patients with resected BRAF V600E– or BRAF V600K–mutant stage III melanoma.

The COMBI-AD trial supported the U.S. Food and Drug Administration approval of adjuvant dabrafenib plus trametinib in resected stage III melanoma with BRAF V600E or BRAF V600K mutations.

Study Details

In the double-blind trial, 870 patients were randomly assigned to receive oral dabrafenib (150 mg twice daily) plus oral trametinib (2 mg once daily) or matching placebos for 12 months. Health-related quality of life—a prespecified exploratory endpoint—was assessed with the European Quality of Life 5-Dimensions 3-Levels (EQ-5D-3L) questionnaire in the intention-to-treat population.

Patient-reported outcomes were assessed at baseline and every 3 months during treatment. During follow-up, patients without disease recurrence were assessed every 3 months for the first 24 months and every 6 months thereafter until study completion, withdrawal, or death.

Changes in Patient-Reported Outcomes

Median follow-up was 34 months in the dabrafenib-plus-trametinib group and 33 months in the placebo group. During the 12-month treatment phase, no statistically significant or clinically meaningful changes from baseline between groups in EQ-5D-3L visual analog scale (EQ-VAS) or utility scores were observed. No clinically meaningful differences in VAS scores or utility scores were observed in the dabrafenib-plus-trametinib group between patients who did vs did not experience the most common adverse events.

During long-term follow-up ranging from 15 to 48 months, VAS and utility scores in the two treatment groups were similar and did not differ from baseline scores. In both the dabrafenib/trametinib group (mean change = −6.02, P = .0032) and the placebo group (mean change = −6.84, P < .0001), significant decreases in VAS scores were observed at disease recurrence, as were significant decreases in utility score (mean changes = −0.0626, P < .0001, and −0.0748, P < .0001, respectively).

The investigators concluded, “These findings show that dabrafenib plus trametinib did not affect patient-reported outcome scores during or after adjuvant treatment, and suggest that preventing or delaying relapse with adjuvant therapy could be beneficial in this setting.”

Dirk Schadendorf, MD, of the Department of Dermatology, University Hospital Essen, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was supported by Novartis. The study authors’ full disclosures can be found at

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.