Kluger HM, et al. - In phase II clinical trial, researchers presented long-term follow-up of pembrolizumab-treated patients with new or progressing brain metastases. Findings revealed that pembrolizumab is active in melanoma brain metastases with acceptable toxicity and durable responses. Multidisciplinary care is needed to manage patients with brain metastases in an optimal manner, including consideration of radiation to large or symptomatic lesions excluded from this trial. Two-year survival was comparable to patients treated with anti-programmed cell death 1 agents without brain metastasis. Data reported that concordant brain and extracerebral responses support the treatment of small, asymptomatic brain metastases with pembrolizumab.

Methods

• For this investigation, 23 patients with melanoma with one or more asymptomatic, untreated 5- to 20-mm brain metastasis not requiring corticosteroids were enrolled; 70% of patients had prior systemic therapy.
• Pembrolizumab was given up to 24 months.
• By modified Response Evaluation Criteria in Solid Tumors (RECIST), brain metastasis response, the primary end point, was evaluated.
• Pretreatment tumors for T-cell infiltrate and programmed death ligand 1 were analyzed.

Results

• Six patients (26%) had a response to brain metastasis.
• Eight patients (35%) did not have a protocol evaluation scan and were not valuable for brain metastasis response due to progression or radiation requirement.
• Metastasis of the brain and systemic responses were consistent at 24 months.
• The median progression-free and total survival times were respectively 2 and 17 months.
• At 24 months, 11 patients (48%) were alive.
• Three patients were invaluable.
• It was noted that one of these three patients had hemorrhaged and two had perilesional edema symptoms requiring radiosurgery, but all three patients continued to have commercial pembrolizumab more than 24 months later.
• Data reported that none of the 24-month survivors received subsequent BRAF inhibitors.
• Neurologic adverse events occurred in 65% of patients; all but one adverse event was grade 1 or grade 2.
• There were three patients with seizures treated with anticonvulsants.
• Findings revealed that most responders had higher pretreatment tumor CD8 cell density and programmed death ligand 1 expression, while not all respondents.