Pembrolizumab Active in Some Lung Cancer Brain Metastases

Pembrolizumab has shown activity against some lung cancer metastases in the brain, but responses can be discordant with extracranial tumor responses.

Some previously untreated metastatic brain tumors in patients with programmed death ligand 1 (PD-L1)–positive non–small-cell lung cancer (NSCLC) have durable responses to pembrolizumab immunotherapy, suggest findings from a small phase II clinical study (abstract 2009) presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 1–5 in Chicago.

“Pembrolizumab can result in durable benefit and long-term survival in patients with untreated brain metastases from NSCLC, with 31% of patients living more than 2 years after initiation of therapy,” reported Sarah B. Goldberg, MD, MPH, and her coauthors at the Yale School of Medicine in New Haven, Connecticut.

Brain metastases are common in patients with advanced lung cancer, and surgery or radiation therapy can delay the initiation of systemic treatment. Anti–programmed death 1 (PD-1) immune checkpoint inhibition with pembrolizumab is now a standard treatment option for these patients, but its activity in the brain and effects on brain metastases are poorly understood.

The authors sought to evaluate the activity and safety of pembrolizumab in patients who have previously untreated NSCLC-derived brain metastases. Eligibility criteria included the presence of at least one untreated brain metastasis measuring between 5 and 20 mm, without neurologic symptoms, and a performance status score of 0 or 1. Patients requiring systemic corticosteroid therapy were excluded from the study.

Thirty-nine patients were divided into two study cohorts: those who were positive for PD-L1 expression and those who were PD-L1–negative (n = 34) or those whose PD-L1 expression status could not be determined (n = 5). Patients received pembrolizumab (10 mg/kg) every 2 weeks.

Among evaluable PD-L1–positive patients, 10 (29%) exhibited brain metastasis responses to pembrolizumab (with a median duration of central nervous system (CNS) response of 7.5 months), compared with none of the PD-L1–negative patients.

Seven patients had discordant responses between the CNS and other organ responses (four with progression in the brain but partial responses elsewhere in their body, and three with partial responses in brain metastases but disease progression elsewhere).

“Treatment was well tolerated and the toxicity profile was consistent with other trials of pembrolizumab,” the authors reported.

Most neurologic adverse events were grade 1 or 2, and no treatment-related neurologic toxicities were reported with a grade higher than 1. Two patients experienced grade 3 pneumonitis.

Median overall survival among PD-L1–positive patients was 9.4 months, and was 8.9 months among all patients regardless of PD-L1 status (95% CI, 6.6–29.7 months).