Factors affecting treatment by BRAF inhibitors in melanoma

The authors aimed to analyze the factors that could predict resistance to BRAF inhibitor therapy in advanced melanoma. The authors found out that levels of certain proteins and the presence of a type of immune cell could predict the occurrence of resistance. 

In advanced melanoma (stages 3 or 4), cancer spreads from the skin to other parts of the body. Targeted therapy has shown improved outcomes in these stages of the disease. Targeted therapy attacks specific genes such as BRAF. These genes are often mutated in melanoma patients. BRAF inhibitors such as dabrafenib (Tafinlar) and vemurafenib (Zelboraf) are examples of targeted therapy. However, patients often have shown resistance to BRAF inhibitors.

Research has found that levels of PD-1 (a protein in the immune system) and the presence of tumor-infiltrating mononuclear cells (TIMC; another type of immune cell) may contribute to the resistance to BRAF inhibitor therapy.

The current study examined the association between PD-1, TIMC, and BRAF inhibitor resistance. 

80 patients with advanced melanoma were included in the study. 46 patients received vemurafenib. 34 patients received dabrafenib. Levels of PD-1 and TIMC were measured .

The protein PD-1 was detected in 35% of patients overall. Patients without PD-1 in tumors had a 10.5 times higher chance of having better response to treatment. The presence of TIMC was associated with a 6.5 times higher chance of having better response to treatment.  

The average progression-free survival (PFS; time following treatment before the disease progressed) was 10 months. The average overall survival (time from treatment until death from any cause) was 15 months. Patients with measurable PD-1 levels had 4.3 times the risk of reduced PFS. The absence of TIMC was associated with 2.5 times the risk of a shorter PFS.

The authors concluded that presence of TIMC and absence of PD-1 resulted in better outcome in melanoma patients treated with BRAF inhibitors.