Treatment for various BRAF melanoma mutations

Molecular genetic tests allows to determine differences in BRAF gene mutations. It defines the treatment effectiveness for melanoma. New study revealed that there are differences between the BRAF genotypes in melanoma mutation – V600K and V600E. It leads to different responses for targeted therapy and immunotherapy.

Targeted therapy with BRAF melanoma mutations – V600

Patients who have a BRAF V600K melanoma mutation are less amenable to targeted therapy with BRAF / MEK inhibitors. At the same time, when BRAF mutation V600E is present, it can make for effectively melanoma treating in this case.

The first part involved 93 patients with advanced melanoma. Patients with different BRAF mutations were given targeted treatment with BRAF / MEK inhibitors, along with an assessment of the treatment effectiveness.

Prof. Schachter – Head of Melanoma Institute – Appointment online   

BRAF genotypes – V600K and V600E have a unique molecular profile:

BRAF V600K mutation has a lower expression of the ERK signaling pathway, a greater expression of the P13AKT genes and a significantly greater mutation load (a quantitative indicator characterizing the mutations number in 1 megabase of the tumor cell genome encoding). Thus, it is less susceptible to the BRAF / MEK suppression.

The BRAF V600E has a more extensive activation of the ERK signaling pathway, and also shows a good response to the BRAF / MEK suppression.

It was noted that in combination therapy with BRAF / MEK suppression, the patients majority in the V600K mutation group in relation to the V600E group shows:

• low response treatment rate – 31% and 52%
• low full response rate – 0% and 10%.

Patients had the following survival rates in subgroups:

• V600K – median survival – 5.7 months;
• V600E – median survival – 7.1 months, while about 20% remained without melanoma progression signs of after five years.

Despite these numerical differences in response rates and progression-free survival, overall survival was similar in both groups. This part of the study confirmed the results of the previous study, and shows that melanoma with the V600K mutation has a lower response rate and a shorter survival rate when treated with targeted therapy with BRAF / MEK inhibitors.

Immunotherapy with BRAF melanoma mutations – V600

At the second study stage, 103 patients with melanoma who received immunotherapy with pembrolizumab or nivolumab were enrolled.

Researchers conducted an unrelated sample with a BRAF melanoma mutation among these patients:

• V600E – 84 patients;
• V600K – 19 patients.

Response to immunotherapy based on the BRAF genotype correlated with clinical expectations. Median follow-up was lasting 31.7 months. After this researchers found a tendency for a higher response level to immunotherapy in patients with V600K mutations compared to V600E – 53% versus 29%. In addition, progression-free survival was longer in patients with the BRAF mutation subtype V600K – 19 versus 2.7 months. However, overall survival was not significantly different – 20.4 vs. 11.7 months.

The second study part showed the best results in immunotherapy with BRAF melanoma mutation V600K.

Source: E-MED, Israel.