Pembrolizumab Appears Effective on Brain Metastases in Melanoma, NSCLC

Pembrolizumab demonstrated an acceptable safety profile and effectiveness upon brain metastases in patients with melanoma or non-small cell lung cancer (NSCLC), a study published in the journal The Lancet Oncology has shown.¹

Immunotherapy targeting the PD-1 axis has activity in several tumor types, including melanoma, NSCLC, head and neck cancer, and endometrial cancer. Researchers explored the activity and safety of the PD-1 inhibitor pembrolizumab in patients with untreated brain metastases from melanoma or NSCLC.

For the open-label, phase 2 trial, investigators enrolled 18 patients with melanoma and 18 with NSCLC with untreated brain metastases, each of whom were receiving care at Yale Cancer Center in New Haven, Connecticut. Patients had at least 1 untreated or progressive brain metastasis between 5 and 20 mm in diameter without associated neurological symptoms or the need for corticosteroids.

Only patients with NSCLC had tumor tissue positive for PD-L1 expression. All patients received pembrolizumab 10 mg/kg IV every 2 weeks until disease progression.

Results showed that a brain metastasis response was achieved in 22% (95% CI, 7-48) of patients with melanoma and 33% (95% CI, 14-59) of patients with NSCLC. Researchers found that responses were durable, with only one NSCLC patient exhibiting an ongoing response at the time of data cut-off.

The most common treatment-related serious and grade 3 to 4 adverse events in the NSCLC cohort were grade 3 colitis, grade pneumonitis, grade 3 fatigue, grade 4 hyperkalemia, and grade 2 acute kidney injury. The only adverse event in the melanoma cohort was 1 case of grade 3 elevated aminotransferases.

Three patients with melanoma experienced clinically-significant neurologic adverse events, including transient grade 3 cognitive dysfunction and grade 1 to 2 seizures.

The findings suggest there might be a role for systemic immunotherapy in patients with untreated or progressive brain metastases.                        

Reference

1. Goldberg SB, Gettinger SN, Mahajan A, Chiang AC, Herbst RS, Sznol M, et al. Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial [published online ahead of print June 3, 2016]. Lancet Oncol. doi: 10.1016/S1470-2045(16)30053-5.