The RATIONALE study: Outcomes of targeted therapy for metastatic melanoma in Russia
TL;DR
In real-world clinical practice, BRAF/MEK targeted therapy has demonstrated effectiveness in the Russian patient population, with outcomes consistent with those observed in randomized clinical trials, despite substantial population heterogeneity and the inclusion of patients with unfavorable prognostic factors.
Abstract
Introduction. The efficacy of targeted therapy with the combination of dabrafenib and trametinib in patients with metastatic cutaneous melanoma harboring BRAF mutations has been demonstrated in randomized clinical trials (COMBI-d/v, COMBI-i) and confirmed in real-world clinical practice. The present study aimed to evaluate survival outcomes, tolerability, and treatment modification rates, taking into account the characteristics of clinical practice and the patient population in Russia. The findings are important for optimizing therapeutic strategies and improving the quality of healthcare. Aim. To evaluate the efficacy and safety of dabrafenib plus trametinib in Russian patients with metastatic cutaneous melanoma harboring BRAF V600 mutation in a real-world setting. Materials and methods. RATIONALE is a prospective, non-interventional, multicenter study. A total of 283 patients with unresectable stage IIIC-D and IV melanoma were included. Patients aged ≥ 18 years with metastatic cutaneous melanoma initiated dabrafenib plus trametinib no more than 4 weeks prior to enrolment. The follow-up period was 1 year. Results. Elevated LDH levels were observed in 33.3% of patients, metastases in ≥ 3 organs in 26.5%, and CNS involvement in 18.4%. The 1-year progression-free survival rate was 54% (95% CI: 48–61%), and overall survival was 78% (95% CI: 73–83%). The objective response rate reached 58.0%, with a median time to response of 3.2 months. Adverse events were reported in 35.7% of patients (grade ≥ 3: 12.0%); the most common was pyrexia (16.6%; grade ≥ 3: 4.2%). Treatment discontinuation due to adverse events occurred in 4.6% of patients. Conclusion. In real-world clinical practice, BRAF/MEK targeted therapy has demonstrated effectiveness in the Russian patient population, with outcomes consistent with those observed in randomized clinical trials, despite substantial population heterogeneity and the inclusion of patients with unfavorable prognostic factors.