Rationale for Immunotherapy in Melanoma Regardless of BRAF Status

Source: Targeted Oncology, May 2023

Marc S. Ernstoff, MD, chief for the ImmunoOncology branch of the Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis at the National Cancer Institute, discusses why physicians would treat metastatic melanoma with immunotherapy prior to small molecule inhibitors in most cases.

The immune checkpoint inhibitors pembrolizumab (Keytruda) and nivolumab (Opdivo) have shown durable, long-term disease control for melanoma. Nivolumab combined with ipilimumab (Yervoy) or nivolumab/relatlimab (Opdualag) extend survival, though with added toxicity.

In patients with BRAF V600 mutations, a BRAF/MEK inhibitor combination is also effective in targeting the MAP kinase pathway. The DREAMseq trial (NCT02224781) investigated the sequence of nivolumab/ipilimumab and dabrafenib (Tafinlar)/trametinib (Mekinist). Patients with BRAF V600 mutations who received nivolumab/ipilimumab first had superior overall survival to those who received the BRAF/MEK targeted therapy combination first.