Encorafenib with binimetinib efficacy in the first, second, and third line of treatment for patients with advanced melanoma harboring a BRAF mutation — real-world study

Introduction. In patients with advanced melanoma with BRAF mutation, the BRAF and MEK inhibitors can be used before or after immunotherapy, and even as third-line systemic treatment. To date, majority of available data on encorafenib plus binimetinib comes from clinical trials. Material and methods. This was a multicenter retrospective study, which aimed to investigate the efficacy of encorafenib plus binimetinib (E+B) treatment in patients with unresectable stage III or IV melanoma in the real-world setting. The study did not include patients treated with adjuvant intent. Progression-free survival (PFS) and overall survival (OS) estimates were obtained using Kaplan-Meier method. Results. There were 130 patients treated in the first-line setting. Their median follow-up was 24.1 (95% CI 20.9–32) months. Median age of the group treated with E+B first line treatment was 63.5 years and LDH level was abnormal in 53.1% of cases, while 25.4% of patients had brain metastases. The median PFS was 10.3 (95% CI 8–12.4) months, 1- and 3-year PFSs were 40.1% (95% CI 31.9–50.3) and 12.3% (95% CI 6.1–24.7), while the objective response rate (ORR) was 58.5%. After the progression of the disease, 32 (24.6%) patients received second-line treatment (including immunotherapy in 28, 87.5% cases) and 5 (3.8%) patients received third-line treatment. The median OS from the start of the first-line treatment was 15.8 (95% CI 12–23.5) months, while the 1-year and 3-year OS rates were 58% (95% CI 49.6–67.9) and 20% (95% CI 11.9–33.6), respectively. In the second-line treatment, after the anti-PD-1-based first-line treatment, the E+B was administered in 82 patients. The median PFS was 8.5 (95% CI 6.5–12) months, and the ORR was 42 (51.2%). The median OS from the start of the second-line treatment was 13.2 (95% CI 10.9–22) months. In the third-line treatment, E+B was used in 23 patients, with 6- and 12-month PFS being 23% (95% CI 10.7–49.6), and 13.8% (95% CI 4.8–39.4), respectively. The median PFS in third-line setting was 3.6 (95% CI 2.8–5.3) months. Conclusions. This real-world evidence supports the clinically meaningful efficacy of the combination of E+B in first-, second- and third-line treatment.