Combination Therapy Increases Survival in Melanoma Patients

Treatment with dabrafenib and trametinib extends patient survival more than 2 years.

Results from a trial for a combination of 2 targeted therapies to treat advanced melanoma have shown an increase in patient survival of more than 2 years compared with vemurafenib monotherapy.

Of the patients involved in the study, 51% are alive after 2 years of receiving the combination therapy, compared with 38% of patients receiving vemurafenib alone.

Analysis of data up to March 13, 2015 showed a median overall survival time among patients with metastatic melanoma of 25.6 months. Among those patients that only received treatment with vemurafenib, survival time was 18 months. On the basis of this finding, the European Commission approved the combination of dabrafenib and trametinib for use in Europe for these patients on September 1, 2015.

“We observed a statistically significant reduction of 34% in the risk of death among patients receiving the combination therapy,” said Professor Caroline Robert, of the Institut Gustave Roussy, Paris, France. “The increased survival among these patients is remarkable, and this median overall survival of more than two years is the longest in this category of patients in a phase III randomized trial.”

Patients with the V600E or V600K mutations of the BRAF gene were randomized in the COMBI-v phase III trial to receive either 150 mg dabrafenib twice daily and 2 mg trametinib once daily, or 960 mg vemurafenib alone twice daily.

By March 2015, 50% of patients had died and the researchers followed the patients for approximately 18 months at the time of death.

“Since our last report from this trial we have an additional 11 months of follow-up and 127 more deaths. This provides data that are mature enough to demonstrate definitively that effect on overall survival and the benefit to patients,” Professor Robert said.

The results also illustrated that patients survived longer and without disease progression than patients receiving vemurafenib alone: 12.6 and 7.3 months respectively.

“The 12.6 months of progression-free survival for patients on the combination treatment is the longest achieved in a randomized study for patients with the BRAF V600 mutation to date,” Robert said.

Rates of severe side effects were similar in both groups of patients, with no unexpected effects presenting during the longer follow-up. Results from an associated study of the patients’ health-related quality-of-life showed significant improvements among those receiving the combination treatment, compared with those receiving vemurafenib. Overall health, physical and social functioning, and symptoms such as pain, insomnia, loss of appetite, diarrhea, and fatigue were all also improved.

“This combination therapy is already available in the US and now also in Europe as a result of the European Commission’s decision to approve its use. This long-term benefit in terms of overall survival confirms the major potential of this combination in patients with metastatic melanoma. A further question to investigate is the combination treatment versus new immunotherapies or combined with them,” Robert concluded.