MAPK Inhibitor Combo Produces 2-Year Overall Survival in Metastatic Melanoma

A median overall survival of longer than 2 years was achieved in a group of patients with metastatic melanoma assigned to treatment with the combination of two MAPK inhibitors, dabrafenib and trametinib, according to the results of a study published recently in the Journal of Clinical Oncology. In fact, results showed that as many as one in five patients treated with the combination remained free of progression at 3 years.

“The combination has an acceptable long-term safety profile and is a standard of care for patients with BRAF mutation–positive metastatic melanoma, particularly given the recent publications demonstrating a significant improvement in the progression-free survival and overall survival in phase III trials of combination vs single-agent BRAF inhibitors,” wrote Georgina V. Long, MD, PhD, of the University of Sydney and Melanoma Institute Australia, and colleagues.

Long and colleagues conducted an analysis of data taken from a four-part phase I/II study that included combination treatment with dabrafenib and trametinib. The analysis included 78 patients with BRAF inhibitor-naive melanoma who were treated with dabrafenib 150 mg twice daily plus trametinib 2 mg daily from the non-randomly assigned part of the study (part B; n = 24) and the randomly assigned part of the study (part C; n = 54).

Patients in part B had a median follow-up of 47.11 months and those in part C, a median of 45.59 months.

The median progression-free survival for patients in part B was 10.8 months and the median overall survival was 27.4 months. Patients in part C had a median progression-free survival of 9.4 months with a median overall survival of 25 months.

Patients from part B had a progression-free survival of 44% at 1 year, 22% at 2 years, and 18% at 3 years and overall survival of 72%, 60%, and 47%, respectively. Patients from part C had progression-free survival of 41% at 1 year, 25% at 2 years, and 21% at 3 years, and a median overall survival of 80%, 51%, and 38%, respectively.

The researchers analyzed the baseline characteristics of patients who progressed with those who did not. They found that normal baseline lactate dehydrogenase (LDH) was significantly associated with continued long-term response without progression compared with elevated LDH (P = .024).

“Consistently, good prognostic features at baseline were associated with both durable ongoing responses and prolonged overall survival and included normal LDH, earlier-stage melanoma, and fewer metastatic sites,” the researchers wrote.

Patients with normal LDH at baseline had a median overall survival of 45.5 months compared with 16.6 months for patients with an elevated LDH.

“Although this analysis is limited, as it is post hoc and in small numbers of patients, these findings are consistent with those from studies of other systemic drug therapies, which have shown that good prognostic features are associated with better clinical outcomes and may be predictive,” the researchers wrote.