Abstract
Simple SummaryAdvanced melanoma is a highly aggressive disease with a poor prognosis. Recent clinical trials have shown that targeted therapy (TT) and immunotherapy (IT) lead to significant improvements in responses to treatment and the survival of advanced melanoma patients. However, little information is available in the form of real-world data on treatment patterns and clinical outcomes for patients with advanced BRAF V600 mutant melanoma. To approach this issue, we performed a retrospective study that involved 382 patients with advanced BRAF V600 mutant melanoma, who received TT in twelve medical centers. Our objectives were to evaluate clinical outcomes in real-world settings, as well as treatment patterns, adverse events, objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). Considering these parameters, the results demonstrated the effectiveness of combined TT with BRAF plus MEK inhibitors in patients with brain metastases and across all lines of therapy, which was well-tolerated and manageable and showed a high safety profile.Clinical trials of targeted therapy (TT) and immunotherapy (IT) for highly aggressive advanced melanoma have shown marked improvements in response and survival rates. However, real-world data on treatment patterns and clinical outcomes for patients with advanced BRAF V600 mutant melanoma are ultimately scarce. The study was designed as an observational retrospective chart review study, which included 382 patients with advanced BRAF V600 mutant melanoma, who received TT in a real-world setting and were not involved in clinical trials. The data were collected from twelve medical centers in Russia. The objective response rates (ORRs) to combined BRAFi plus MEKi and to BRAFi mono-therapy were 57.4% and 39.8%, respectively. The median progression-free survival (PFS) and median overall survival (OS) were 9.2 months and 22.6 months, respectively, for the combined first-line therapy; 9.4 months and 16.1 months, respectively, for the combined second-line therapy; and 7.4 months and 17.1 months, respectively, for the combined third- or higher-line therapy. Analysis of treatment patterns demonstrated the effectiveness of the combined TT with BRAF plus MEK inhibitors in patients with brain metastases, rare types of BRAF mutations, and across lines of therapy, as well as a well-tolerated and manageable safety profile.
Highlights
Advanced melanoma was considered to be a chemotherapy-resistant malignancy with a poor prognosis and a median overall survival of less than 12 months
Patients were divided into two subgroups depending on the type of targeted therapy: BRAF inhibitor monotherapy (BRAFi) or combination therapy with BRAFi and MEKi
The ADMIRE study demonstrated that targeted therapy showed high effectiveness in routine clinical practice, in particular in patients with unfavorable prognostic factors, such as brain metastases, which were detected in over half of patients (52.6%) at the initiation of TT
Summary
Advanced melanoma was considered to be a chemotherapy-resistant malignancy with a poor prognosis and a median overall survival (mOS) of less than 12 months. Used therapies have included cytotoxic chemotherapies and cytokine-based immunotherapy (interferon, interleukin-2), which were primarily palliative in nature, with no improvements in survival. In the last 10 years, new effective therapies have emerged which focus either on the BRAF V600E mutation (targeted BRAF-directed therapy) or against regulatory checkpoints (immunotherapy with checkpoint inhibitors). The advent of targeted therapy and checkpoint inhibitors has dramatically changed the landscape of treatment for metastatic melanoma. Rapid progress in BRAF and MEK targeted therapy (TT) and immunotherapy (IT) has led to significant improvements in objective response and survival rates in advanced melanoma patients [7,8,9,10,11,12,13,14,15]
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