362P - Melanoma with V600 BRAF mutations and brain metastases. Experience of targeted therapy in a single center.

Date 10 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Anti-Cancer Agents & Biologic Therapy
Melanoma and other Skin Tumours
Personalised Medicine
Presenter David Naskhletashvili
Citation Annals of Oncology (2017) 28 (suppl_5): v109-v121. 10.1093/annonc/mdx366
Authors D. Naskhletashvili1, L. Demidov2
  • 1Neurooncology, N. N. Blokhin Russian Cancer Research Center, 115478 - Moscow/RU
  • 2Department Of Dermatology, N. N. Blokhin Russian Cancer Research Center, 115478 - Moscow/RU

Abstract

Background

The effectiveness of chemotherapy (temozolomide, fotemustine, lomustine) alone and in combination with whole brain irradiation in patients with melanoma with cerebral metastases does not exceed 7-10%, without significant impact on overall survival, which is 2-4 months. Targeted therapy has improved the survival of patients with metastatic melanoma with BRAF V600 mutations. In patients with brain metastases targeted therapies allow not only to control systemic tumor process, but also to achieve the effect of treatment of cerebral metastases. So, the efficacy (complete and partial regressions of brain metastases) targeted therapy with BRAF inhibitors vemurafenib or dabrafenib in patients with melanoma with BRAF V600 mutations in metastatic brain lesions, according to the literature, varies from 18.0% to 39.2%, with a median survival of patients from 5,3 to 8,2 months. We evaluated the efficacy of targeted therapy (BRAF inhibitors vemurafenib or dabrafenib as monotherapy and also in combinations with MEK inhibitors cobimetinib or trametinib) in patients with melanoma brain metastases.

Methods

In Russian N.N. Blokhin Cancer Research Center effect of the various schemes targeted therapy were evaluated in 45 patients with melanoma with BRAF V600 mutations and brain metastases. Patients received the following treatment options: dabrafenib (4 patients), dabrafenib + trametinib (11 patients), vemurafenib (25 patients), vemurafenib + cobimetinib (5 patients). Three patients (6,7%) targeted therapy was combined with whole brain irradiation, in eight patients (17,8%) – in combination with stereotactic radiotherapy/radiosurgery.

Results

Complete regression of brain metastases was achieved in 3 patients (6,7%), partial regression in 19 (42,2%), stabilization in 15 (33,3%). Thus, the tumor control in the brain was observed in 37 patients (82,2%). In 43 patients (95,6%) of 45 were also established metastases in other sites (extracranial lesions). Complete regression of metastases in extracranial lesions was achieved in 1 patient (2,3%), partial regression – in 26 (60,4%), stabilization in 13 (30,2%). The median time to disease progression was 5.5 months. The median survival of patients was 8,5 months.

Conclusions

The data presented indicate that the targeted therapy with BRAF inhibitors as monotherapy and also in combination with MEK inhibitors in patients with metastatic melanoma with brain metastases provides control over the disease in most patients and has a significant advantage with a group of historical control (chemotherapy ± whole brain irradiation).

Clinical trial identification

Legal entity responsible for the study

Russian N.N. Blokhin Cancer Research Center

Funding

Russian N.N. Blokhin Cancer Research Center

Disclosure

All authors have declared no conflicts of interest.