Dr Eroglu on the Study of Encorafenib Plus Binimetinib/Nivolumab in BRAF V600+ Melanoma With Brain Metastases

“If [a patient with] melanoma has a BRAF mutation, there could be a consideration of this triplet approach of combining targeted therapy with immunotherapy, as I think it may be a therapeutically helpful regimen for these patients, as opposed to starting them with immunotherapy alone.”

Zeynep Eroglu, MD, medical oncologist in the Department of Cutaneous Oncology at Moffitt Cancer Center and an assistant professor in the Department of Oncologic Sciences at the University of South Florida Morsani College of Medicine, discussed the rationale for investigating the combination of encorafenib (Braftovi), binimetinib (Mektovi), and nivolumab (Opdivo) compared with ipilimumab (Yervoy) plus nivolumab in patients with BRAF V600–mutant melanoma and brain metastases.

The regimens were evaluated in this patient population during the phase 2 SWOG S2000 trial (NCT04511013). The trial met its primary end point, with patients treated with the triplet (n = 16) experiencing a median progression-free survival (PFS) of 6.2 months (955 CO, 3-14.4) compared with 1.5 months (95% CI, 0.7-1.7) for those given the doublet (n = 15; HR, 0.51; 95% CI, 0.0-0.92; 1-sided P = .07). The median intracranial PFS was 8.7 months (95% CI, 3-19.4) vs 1.5 months (95% CI, 0.7-1.7), respectively (HR, 0.39; 95% CI, 0-0.68; P = .01).

Eroglu emphasized the relevance of these findings for the management of symptomatic brain metastases in melanoma, as this is a patient population often requiring urgent intracranial disease control due to neurologic compromise. She underscored the importance of determining BRAF mutation status early, ideally prior to systemic treatment initiation, to enable timely integration of targeted therapy when appropriate.

According to Eroglu, the higher overall response rate and longer PFS observed with the triplet regimen in SWOG S2000 suggest that encorafenib plus binimetinib and nivolumab may offer therapeutic advantages over ipilimumab plus nivolumab for patients with BRAF V600–mutant symptomatic brain metastases, particularly in cases requiring rapid disease control, although additional study of this regimen is needed. She noted that the combination of targeted therapy with immunotherapy may provide a bridge to durable intracranial responses while maintaining systemic disease control.