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Outcomes in Melanoma With Active Brain Metastases After Treatment With Pembrolizumab

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Key Points

  • Brain metastasis response occurred in 6 of the total 23 patients, although 8 patients were not evaluable for brain response.
  • Brain and extracerebral responses were concordant, with all responses ongoing at 24 months.

As reported in the Journal of Clinical Oncology by Kluger et al, pembrolizumab (Keytruda) showed activity in brain metastases in patients with melanoma enrolled in a phase II study.

The study included 23 patients with melanoma with one or more asymptomatic untreated 5- to 20-mm brain metastasis not requiring corticosteroid treatment. Prior systemic therapy had been received by 70% of patients.

Pembrolizumab at 10 mg/kg every 2 weeks was given for up to 24 months. The primary endpoint was brain metastasis response assessed by modified Response Evaluation Criteria in Solid Tumors criteria.

Brain and Extracerebral Responses

Overall, brain metastasis response was observed in 6 (26%) of the total of 23 patients, with complete response in 4. Of the 23 patients, 8 (35%) did not reach a protocol evaluation scan and were nonevaluable for brain response as a result of progression or need for radiation therapy. Among the 15 patients evaluable for extracerebral response, response was observed in 7 patients, including 4 with complete response and 3 with partial response. The brain and systemic responses were concordant, and all were ongoing at 24 months.

Among all patients, median progression-free and overall survival durations were 2 and 17 months, respectively. Eleven patients (48%) were alive at 24 months, with this group including 3 of the nonevaluable patients. Among these 3, 1 had a hemorrhage and 2 had symptoms from perilesional edema requiring radiosurgery; all 3 patients remained on commercial pembrolizumab (2 mg/kg or 200 mg every 3 weeks) more than 24 months later.

None of the patients surviving 24 months received subsequent BRAF inhibitors. Most responders, but no nonresponders, had higher tumor CD8 cell density and programmed cell death ligand 1 expression.

Toxicity

Neurologic adverse events occurred in 65% of patients, with all adverse events but 1 being grade 1 or 2. Three patients had seizures, which were treated with anticonvulsants. Grade 3 adverse events occurring in 1 patient each included hepatitis, hyponatremia, acidosis, and rash.

The investigators concluded, “Pembrolizumab is active in melanoma brain metastases with acceptable toxicity and durable responses. Multidisciplinary care is required to optimally manage patients with brain metastases, including consideration of radiation to large or symptomatic lesions, which were excluded in this trial. Two-year survival was similar to patients without brain metastasis treated with anti–programmed cell death 1 agents. Concordant brain and extracerebral responses support use of pembrolizumab to treat small, asymptomatic brain metastases.”

The study was supported in part by Merck and the Yale Cancer Center, with additional support provided by National Institutes of Health grants.  

Harriet M. Kluger, MD, of the Yale University School of Medicine and Yale Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: See study authors’ full disclosures at jco.ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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