Combined targeted therapy with dabraphenib +trametinib in treatment of melanoma patients with V600 BRAF mutations and brain metastases


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Abstract

The effectiveness of traditional chemotherapy (temozolomide, fotemustine, lomustine) alone and in combinations with radiotherapy for the entire brain in melanoma patients with brain metastases does not exceed 7-10% without significant effect on overall survival, which is 2-4 months. Targeted therapy improved the survival of patients with disseminated melanoma and BRAF-V600 mutations. In patients with brain metastases, targeted drugs allow not only to control the systemic tumor process, but also achieve an effect in the treatment of brain metastases. Thus, according to the published data, the effectiveness of targeted therapy using BRAF inhibitors vemurafenib and dabrafenib in melanoma patients with BRAF V600 mutations and metastatic brain lesions reaches 18.0-39.2%, with a median survival of patients ranging from 5.3 to 8, 2 months. Data on the effectiveness of combined targeted therapy (BRAF inhibitors + МЕК inhibitors) in melanoma patients with brain metastases are not yet available in the literature. In the RORC n.a. N.N. Blokhin, a study aimed to the evaluation of the efficacy of combined targeted therapy with the inclusion of BRAF inhibitor dabrafenib and МЕК inhibitor trametinib in melanoma patients with brain metastases is under way. According to preliminary data of study, partial regression of brain metastases was achieved in 36.3% of patients, stabilization of the disease - in 27.3% of cases. The median time to progression of the disease was 5.0 months, the median overall survival was 8.5 months. The data presented indicate that the use of a combination of dabrafenib and trametinib in melanoma patients with metastatic brain lesions can provide disease control in most patients and has a significant advantage over standard chemo- and radiotherapy for the entire brain. It is necessary to conduct further studies of combined targeted therapy as the first-line antitumor drug treatment for melanoma patients with BRAF-V600 mutations and metastatic brain lesions.

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About the authors

D. R Naskhletashvili

FSBI RORC n.a. N.N. Blokhin of RMH

Email: nas-david@yandex.ru
PhD, Senior Researcher at the Neurosurgical (Oncological) Department

V. A Gorbunova

FSBI RORC n.a. N.N. Blokhin of RMH

A. Kh Bekyashev

FSBI RORC n.a. N.N. Blokhin of RMH

L. V Demidov

FSBI RORC n.a. N.N. Blokhin of RMH

G. Yu Kharkevich

FSBI RORC n.a. N.N. Blokhin of RMH

I. V Samoylenko

FSBI RORC n.a. N.N. Blokhin of RMH

K. A Baryshnikov

FSBI RORC n.a. N.N. Blokhin of RMH

K. V Orlova

FSBI RORC n.a. N.N. Blokhin of RMH

I. A Utyashev

FSBI RORC n.a. N.N. Blokhin of RMH

N. N Petenko

FSBI RORC n.a. N.N. Blokhin of RMH

I. G Markina

FSBI RORC n.a. N.N. Blokhin of RMH

E. A Moskvina

FSBI RORC n.a. N.N. Blokhin of RMH

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