Triple combination of vemurafenib, cobimetinib, and atezolizumab in real clinical practice in BRAF metastatic melanoma: updated 4-year OS analyses

Introduction . Combined immune-targeted therapy is a new registered approach for treating metastatic melanoma. Identifying subgroups of patients who may benefit more from simultaneous rather than sequential administration of triple combination drugs is of current scientific interest to the medical community. Aim . To present a 4-year updated analysis of the efficacy and safety of triple therapy with atezolizumab + vemurafenib + cobimetinib (AVC) in patients with BRAF-mutated advanced melanoma in real-world clinical practice in Russia. Materials and methods . A prospective non-interventional study included 59 patients with metastatic BRAF+ melanoma receiving the triple combination of vemurafenib, cobimetinib, atezolizumab. The primary endpoint was 24-month OS. Additionally, PFS, ORR, and risk factors influencing OS were evaluated. This paper is a 4-year update of a previously published analysis. Results . The median OS in the entire population was 23.67 months (95% CI 13.19–NR), and the median PFS in the entire population was 14.97 months (95% CI 8.00–24.39). An objective response was recorded in 57.6% of patients. Cox multivariate analysis revealed a significant impact of age, presence of lung metastases, and large tumor mass (10–15 cm vs ≤6 cm) on OS. The presence of liver metastases reduced median survival by more than 2.5 times, but no significant effect was proven. BMI, ECOG ≥ 2, CNS metastases, line of therapy, and PD-L1 did not have a statistically significant effect. Conclusion . Triple therapy demonstrates high clinical efficacy in patients with metastatic BRAF+ melanoma in real-world clinical practice in the analyzed population of patients with an unfavorable prognosis – CNS involvement, liver involvement, and second-line and subsequent therapy. Age, the presence of lung metastases, and tumor size were found to be prognostic factors affecting survival.