Dr. Weber on Side Effects of Dabrafenib/Trametinib in Melanoma

Jeffrey S. Weber, MD, PhD, deputy director and co-director of the Melanoma Program at the Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center, 2016 Giant of Cancer Care^® in Melanoma, discusses the side effect profile of dabrafenib (Tafinlar) and trametinib (Mekinist) for patients with melanoma.

The side effects of adjuvant dabrafenib and trametinib have been similar to what has been seen in patients with metastatic disease. However, fatigue and fevers can occur suddenly and be moderately debilitating in the adjuvant setting, which can lead to drug holds or the need for steroids, explains Weber.

Fever and fatigue are the side effects that led to a significant number of treatment discontinuations when this combination was investigated in the COMBI-AD trial. In some patients, these side effects were untreatable and kept returning, says Weber. However, most side effects were well tolerated and treatable.

In the phase III COMBI-AD trial, a doubling in 3-year relapse-free survival (RFS) rates remained consistent across patient subgroups. After a median follow-up of 2.8 years, the 3-year RFS rate with dabrafenib and trametinib was 58% compared with 39% for placebo (HR, 0.47; 95% CI, 0.39-0.58; P <.0001). The 3-year overall survival rate was 86% in the combination arm versus 77% with placebo (HR, 0.57; 95% CI, 0.42-0.79; P = .0006).