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)

Kristina V Orlova, Evgeniy V Ledin, Natalia V Zhukova, Rashida V Orlova, Elena V Karabina, Mikhail V Volkonskiy, Daniil L Stroyakovskiy, Aleksandr N Yurchenkov, Svetlana A Protsenko, Alexey V Novik, Ludmila V Vorotilina, Fedor V Moiseenko, Victor L Chang, Aleksandr I Kazmin, Svetlana A Tkachenko, Sergey V Gamaunov, David R Naskhletashvili, Igor V Samoylenko, Anastasia S Vikhrova, Igor A Utyashev, Galina Yu Kharkevich, Natalia N Petenko, Irina Zh Shubina, Lev V Demidov, Kristina V Orlova, Evgeniy V Ledin, Natalia V Zhukova, Rashida V Orlova, Elena V Karabina, Mikhail V Volkonskiy, Daniil L Stroyakovskiy, Aleksandr N Yurchenkov, Svetlana A Protsenko, Alexey V Novik, Ludmila V Vorotilina, Fedor V Moiseenko, Victor L Chang, Aleksandr I Kazmin, Svetlana A Tkachenko, Sergey V Gamaunov, David R Naskhletashvili, Igor V Samoylenko, Anastasia S Vikhrova, Igor A Utyashev, Galina Yu Kharkevich, Natalia N Petenko, Irina Zh Shubina, Lev V Demidov

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.

Keywords: BRAF; MEK; chart review; cobimetinib; dabrafenib; melanoma; trametinib; vemurafenib.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Targeted therapy results according to the initial LDH levels (p = 0.0156).
Figure 2
Figure 2
Overall survival according to the mutation subtype (p = 0.0268).
Figure 3
Figure 3
Overall survival in patients who received immunotherapy with anti-PD1 agents before or after targeted therapy (p = 0.0061).

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