Optimizing Treatment for Symptomatic Melanoma Brain Metastases

Treatment for symptomatic melanoma brain metastases remains challenging, with limited efficacy from current standard immunotherapies like anti–PD-1 and anti-CTLA4. However, targeted triplet regimens have shown greater promise than doublet regimens in the space, and the randomized phase 2 SWOG S2000 sought to investigate a triplet regimen incorporating BRAF/MEK inhibitors further.

Here, Zeynep Eroglu, MD, discusses the study in an interview with Targeted Oncology^TM. Eroglu is a 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.

The study's primary end point was overall progression-free survival (PFS), encompassing both intracranial and extracranial responses. Patient demographics were well matched between the 2 arms, with approximately 15 patients per arm. Notably, about half of the patients had undergone prior surgery or radiation for their brain metastases, and nearly half were on corticosteroids at the time of enrollment. No significant demographic differences were observed between the groups.

Regarding the findings, the triplet regimen of encorafenib (Braftovi), binimetinib (Mektovi), and nivolumab (Opdivo) demonstrated a significant improvement in overall PFS. The six-month PFS rate was 54% for the triplet arm compared to 20% for the standard ipilimumab-nivolumab arm, with a hazard ratio of 0.47.

Furthermore, the triplet regimen showed substantial benefits in intracranial PFS. The median intracranial PFS was 8.7 months for the triplet arm vs only 1.3 months for the ipilimumab-nivolumab arm. Intracranial response rates were also significantly higher with the triplet regimen at 75% compared with approximately 13% with ipilimumab-nivolumab.

As the first randomized study in this space, S2000 shows that this first-line triplet regimen warrants further study.