Real-World Experience with Targeted Therapy in BRAF Mutant Advanced Melanoma Patients: Results from a Multicenter Retrospective Observational Study Advanced Melanoma in Russia (Experience) (ADMIRE)

SIMPLE SUMMARY: Advanced 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. ABSTRACT: 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.