As reported in The Lancet Oncology by Sarah B. Goldberg, MD, MPH, and colleagues, continued follow-up of the non–small cell lung cancer (NSCLC) cohort of a single-institution phase II trial showed that pembrolizumab produced responses in patients with brain metastases and programmed cell death ligand 1 (PD-L1) expression ≥ 1%.
Sarah B. Goldberg, MD, MPH
Study Details
In the trial, 42 patients at Yale Cancer Center with stage IV disease and at least one brain metastasis measuring 5–20 mm that had not previously been treated or whose disease had progressed after radiotherapy received pembrolizumab at 10 mg/kg every 2 weeks. Patients could have no neurologic symptoms or corticosteroid treatment requirement. The primary endpoint was the proportion of patients achieving a central nervous system (CNS) response on modified Response Evaluation Criteria in Solid Tumors criteria.
Responses
Median follow-up was 8.3 months. Among 37 patients with PD-L1 expression ≥ 1%, CNS response was observed in 11 (29.7%), including complete response in 4 patients. An additional four patients (10.8%) had stable disease. Median duration of response was 5.7 months. Both CNS and systemic response was observed in seven patients (18.9%). Median progression-free survival was 1.9 months, and median CNS progression-free survival was 2.3 months, with 33% of patients remaining progression-free at 1 year. Median overall survival was 9.9 months, with rates of 40% and 34% at 1 and 2 years.
No CNS responses were observed among five patients with PD-L1 expression < 1%.
Adverse Events
Among all 42 patients, treatment-related grade 3 or 4 adverse events occurred in seven (17%), consisting of pneumonitis in two and constitutional symptoms, colitis, adrenal insufficiency, hyperglycemia, and hypokalemia in one each, respectively. Treatment-related serious adverse events occurred in six patients and consisted of pneumonitis in two and acute kidney injury, colitis, hypokalemia, and adrenal insufficiency in one each, respectively. Grade 3 neurologic events irrespective of causal attribution occurred in three patients and consisted of cognitive dysfunction, seizure, and stroke. There were no treatment-related deaths.
The investigators concluded, “Pembrolizumab has activity in brain metastases from NSCLC with PD-L1 expression [of] at least 1% and is safe in selected patients with untreated brain metastases. Further investigation of immunotherapy in patients with CNS disease from NSCLC is warranted.”
Dr. Goldberg, of the Department of Medicine (Medical Oncology), Yale School of Medicine, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Merck and the Yale Cancer Center. For full disclosures of the study authors, visit thelancet.com.
