Pembrolizumab for Untreated/Progressive Brain Metastases in Melanoma or NSCLC

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Sarah B. Goldberg, MD, of Yale University School of Medicine, and colleagues 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 1 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 4 melanoma patients (4.0–10.0 months) and in 5 of the 6 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 3 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. ■

Goldberg SB, et al: Lancet Oncol 17: 976-983, 2016.