Pembrolizumab Active for Untreated/Progressive Brain Metastases in Melanoma or NSCLC


Key Points

  • Brain metastasis responses were observed in both melanoma and NSCLC patients treated with pembrolizumab.
  • Responses were ongoing at 4 to 10 months in melanoma patients and at 3 to 7 months in NSCLC patients.

Goldberg et al found that pembrolizumab (Keytruda) was active in untreated or progressive brain metastases in melanoma and non–small cell lung cancer (NSCLC), according to a single-center phase II trial reported in The Lancet Oncology.

Study Details

The study included 36 patients at Yale Cancer Center, 18 with melanoma and 18 with NSCLC, who had at least one untreated or progressive brain metastasis (between 5 and 20 mm in diameter) without associated neurologic symptoms or the need for corticosteroid treatment. Patients with NSCLC had to have tumor tissue positive for programmed cell death ligand 1 (PD-L1) expression. Patients received pembrolizumab at 10 mg/kg every 2 weeks until disease progression. The primary endpoint was brain metastasis response, and the study is ongoing.


Brain metastasis response was observed in 4 (22%, 95% confidence interval [CI] = 7%–48%) of 18 patients with melanoma (all partial responses) and 6 (33%, 95% CI = 14%–59%) of 18 patients with NSCLC, including 4 complete responses. Responses were ongoing at the time of analysis in each of the four melanoma patients (4.0–10.0 months) and in five of the six NSCLC patients (3.2–7.0 months).

Adverse Events

Treatment-related serious and grade 3 or 4 adverse events were grade 3 aminotransferase elevation (n = 1, 6%) in the melanoma group and grade 3 colitis (n = 1, 6%), grade 3 pneumonitis (6%), grade 3 fatigue (6%), grade 4 hyperkalemia (6%), and grade 2 acute kidney injury (6%) in the NSCLC group. Transient grade 3 cognitive dysfunction or grade 1 or 2 seizure was observed in three melanoma patients (17%).

The investigators concluded: “Pembrolizumab shows activity in brain metastases in patients with melanoma or NSCLC with an acceptable safety profile, which suggests that there might be a role for systemic immunotherapy in patients with untreated or progressive brain metastases.”

The study was funded by Merck and the Yale Cancer Center.

Sarah B. Goldberg, MD, of Yale University School of Medicine, is the corresponding author of The Lancet Oncology article.

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®.