KEY TAKEAWAYS
- The E-BRAIN/GEM1802 phase 2 trial aimed to evaluate the effectiveness and safety of encorafenib plus binimetinib in BRAFV600-mutant melanoma patients with BM.
- The primary endpoint was icRR.
- The results showed that encorafenib plus binimetinib benefited BRAFV600-mutant melanoma patients having BM, with manageable safety and response.
Encorafenib plus binimetinib (EB) represents a standard treatment for advanced BRAFV600-mutant melanoma.
Iván Márquez-Rodas and the team aimed to tevaluate the efficacy and safety of encorafenib plus binimetinib in patients with BRAFV600-mutant melanoma and brain metastasis (BM), and investigate the impact of radiotherapy on response duration.
Patients diagnosed with BRAFV600-mutant melanoma and BM were administered encorafenib at a daily dose of 450 mg alongside binimetinib at 45 mg twice daily. Those achieving partial response or stable disease upon initial tumor assessment were offered radiotherapy. Treatment was maintained until disease progression.
The primary endpoint focused on assessing the intracranial response rate (icRR) following 2 months of encorafenib plus binimetinib therapy, with a predefined futility threshold set at 60%.
About 25 patients without symptoms of BM and 23 patients experiencing BM symptoms, regardless of corticosteroid use, were included, 31 patients ([64.6%]) underwent sequential radiotherapy. After 2 months, the icRR was [70.8% (95% CI: 55.9-83.1)], with [10.4% achieving a complete response].
Median intracranial progression-free survival (icPFS) was [8.5 months (95% CI: 6.4-11.8)], and overall survival (OS) was [15.9 months (95% CI: 10.7-21.4)], with [icPFS of 8.3 months and OS of 13.9 months for patients receiving radiotherapy]. The most common grade 3-4 treatment-related adverse event (TRAEs) was increased alanine aminotransferase (ALT) levels ([10.4%]).
The study concluded that encorafenib plus binimetinib demonstrated significant clinical benefit in terms of icRR and maintained a tolerable safety profile, with a low incidence of severe TRAEs, in BRAFV600-mutant patients with melanoma having BM, including those requiring steroids for symptom management. However, sequential radiotherapy was found to be feasible but did not appear to extend the duration of response.
Funding was provided by the Spanish Multidisciplinary Melanoma Group (GEM) through a grant from Pierre Fabre. The trial was sponsored by the GEM.
Clinical Trial: https://clinicaltrials.gov/study/NCT03898908
Márquez-Rodas I, Álvarez A, Arance A, et al. (2024). “Encorafenib and binimetinib followed by radiotherapy for patients with BRAFV600-mutant melanoma and brain metastases, (E-BRAIN/GEM1802 phase II study).” Neuro-Oncology, 2024; noae116, https://doi.org/10.1093/neuonc/noae116
