VIENNA, AUSTRIA—Latest results from a clinical trial using a combination of two targeted therapies—dabrafenib and trametinib—to treat advanced melanoma have shown that patients are living significantly longer with the combination therapy compared with patients treated with a single drug—vemurafenib. These findings were presented at the 2015 European Cancer Congress.
In addition to the longer median overall survival time for patients receiving the combination treatment, 51% of those patients are still alive after 2 years, compared with 38% of patients receiving vemurafenib. These findings were presented by Professor Caroline Robert, MD, PhD, of the Institut Gustave Roussy, Paris, France.
Analysis of data up to March 13, 2015, showed the median overall survival time for patients with metastatic melanoma harboring V600 mutations in the BRAF gene who received the combination treatment was 25.6 months. Overall survival time for patients receiving vemurafenib was 18 months.
“We observed a statistically significant reduction of 34% in the risk of death among patients receiving the combination therapy,” Robert said. “The increased survival among these patients is remarkable, and this median overall survival of more than 2 years is the longest in this category of patients in a phase III randomized trial.”
These new results come from an analysis of all data from the COMBI-v phase III trial, which randomized previously untreated patients with the V600E or V600K mutations of the BRAF gene to receive either 150 mg dabrafenib twice daily and 2 mg trametinib once a day, or 960 mg vemurafenib twice a day.
By March 2015, approximately 50% (349 of the 704) patients had died and the researchers had followed the patients for approximately 18 months.
“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 the effect on overall survival and the benefit to patients,” said Robert.
The updated analysis also reported that patients receiving the combination treatment survived significantly longer without their disease progressing than did patients receiving vemurafenib: 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,” she said.
Rates of severe side effects remain similar in both groups of patients, with no unexpected effects showing during the longer follow-up. Results from an associated study of the patients’ health-related quality of life showed significant and clinically meaningful improvements among those receiving the combination treatment, compared with those receiving vemurafenib. Overall health, physical and social functioning, and specific symptoms such as pain, insomnia, loss of appetite, diarrhea, and fatigue were all improved.
“This combination therapy is already available in the [United States] 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,” concluded Robert.